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ResearchIn-Press PreviewImmunologyMetabolism Open Access | 10.1172/JCI205170

Balancing lipid synthesis and oxidation promotes B cell response to vaccination during immunosuppression

Elizabeth A. Thompson,1 Alexis Figueroa,1 Katerina Roznik,1 Nicole E. Skinner,2 Santosh Dhakal,3 Shuai Li,4 Luca Biavati,5 Laura A. Sena,5 Laila Stoddart,1 Karli Redinger,3 Samuel B. Warner,1 Sabra L. Klein,1 Nadine Rouphael,6 Joel N. Blankson,1 Yolanda Eby,7 Robert D. Leone,5 Peter S. Heeger,8 Mark A. Robien,9 Christian P. Larsen,10 Erika L. Pearce,5 Edward J. Pearce,3 Hongkai Ji,11 Andrew H. Karaba,1 Dorry L. Segev,1 Aaron A.R. Tobian,1 William A. Werbel,1 Andrea L. Cox,1 and Justin R. Bailey1

1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Division of Infectious Diseases, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, United States of America

3Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

4Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States of America

6Hope Clinic, Infectious Diseases Division, Emory Unviversity, Decatur, United States of America

7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States of America

8Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America

9Transplantation Branch, Division of Allergy Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Rockville, United States of America

10Department of Surgery, Emory University, Decatur, United States of America

11Department of Biostatics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States of America

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Published September 17, 2026 - More info

J Clin Invest. https://doi.org/10.1172/JCI205170.
Copyright © 2026, Thompson et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published September 17, 2026 - Version history
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Abstract

Pharmacologic immunosuppression is essential for preventing organ rejection and controlling autoimmunity, but profoundly impairs humoral immunity, increasing the risk of vaccine failure and infection. The mechanisms by which immunosuppressive therapies disrupt human B cell responses remain poorly defined. Here, we identified dysregulated lipid metabolism as a central determinant of impaired vaccine response in solid organ transplant recipients (SOTRs). Using high-dimensional immune profiling, single-cell transcriptomics, and functional metabolic assays, we found that effective B cell responses required a homeostatic balance between lipid synthesis and fatty acid oxidation. The widely used immunosuppressive agent, mycophenolic acid (MPA) was strongly associated with vaccine non-response and induced excessive lipid synthesis, lipid accumulation, and mitochondrial stress in B cells. In contrast, CD11c+ B cells retained the capacity to differentiate into plasmablasts in the presence of MPA through elevated expression of CPT1A, a mitochondrial fatty acid transporter, and enhanced fatty acid oxidation. These cells were found to be a key feature of early effective vaccine responses in healthy individuals and SOTRs. Notably, pharmacologic inhibition of cholesterol synthesis partially restored plasmablast differentiation in the presence of MPA. These findings identify B cell lipid metabolism as a critical and targetable regulator of human humoral immunity during immunosuppression.

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