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B cells, antibody-secreting cells, and virus-specific antibodies respond to herpes simplex virus 2 reactivation in skin
Emily S. Ford, … , Jia Zhu, Lawrence Corey
Emily S. Ford, … , Jia Zhu, Lawrence Corey
Published March 30, 2021
Citation Information: J Clin Invest. 2021;131(9):e142088. https://doi.org/10.1172/JCI142088.
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Research Article Immunology Infectious disease Article has an altmetric score of 14

B cells, antibody-secreting cells, and virus-specific antibodies respond to herpes simplex virus 2 reactivation in skin

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Abstract

Tissue-based T cells are important effectors in the prevention and control of mucosal viral infections; less is known about tissue-based B cells. We demonstrate that B cells and antibody-secreting cells (ASCs) are present in inflammatory infiltrates in skin biopsy specimens from study participants during symptomatic herpes simplex virus 2 (HSV-2) reactivation and early healing. Both CD20+ B cells, most of which are antigen inexperienced based on their coexpression of IgD, and ASCs — characterized by dense IgG RNA expression in combination with CD138, IRF4, and Blimp-1 RNA — were found to colocalize with T cells. ASCs clustered with CD4+ T cells, suggesting the potential for crosstalk. HSV-2–specific antibodies to virus surface antigens were also present in tissue and increased in concentration during HSV-2 reactivation and healing, unlike in serum, where concentrations remained static over time. B cells, ASCs, and HSV-specific antibody were rarely detected in biopsies of unaffected skin. Evaluation of samples from serial biopsies demonstrated that B cells and ASCs followed a more migratory than resident pattern of infiltration in HSV-affected genital skin, in contrast to T cells. Together, these observations suggest the presence of distinct phenotypes of B cells in HSV-affected tissue; dissecting their role in reactivation may reveal new therapeutic avenues to control these infections.

Authors

Emily S. Ford, Anton M. Sholukh, RuthMabel Boytz, Savanna S. Carmack, Alexis Klock, Khamsone Phasouk, Danica Shao, Raabya Rossenkhan, Paul T. Edlefsen, Tao Peng, Christine Johnston, Anna Wald, Jia Zhu, Lawrence Corey

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Figure 4

Migration kinetics of B and T cells into genital skin during HSV-2 reactivation and tissue healing by type of biopsy and over time.

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Migration kinetics of B and T cells into genital skin during HSV-2 react...
Density of (A) CD20+ cells by IF (n = 11), (B) IgG RNA+ cells by FISH (n = 10), (C) CD4+ T cells by IF (n = 8), and (D) CD8+ T cells by IF (n = 8) in tissue at the biopsy time points (left panels) and by participant over time (right panels). Statistical testing was by Friedman’s test with Dunn’s corrections for multiple comparisons. Each graph on the right presents cell counts from genital-area biopsies over time, as measured from the identified symptomatic lesion. (E) Correlation (r) between B and T cell subsets and between CD20+ and IgG RNA+ cells was calculated by repeated-measure correlation. Participants are labeled by color; results for multiple specimens from genital and control areas from each participant are included in each graph.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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