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CD20+ T follicular helper–like cells drive antigen-specific autoimmunity in bullous pemphigoid
Hui Fang, Shengxian Shen, Kang Li, Tianyu Cao, Bing Wang, Haijun Miao, Ke Xue, Yaxing Bai, Liang Li, Xia Li, Pei Qiao, Jieyu Zhang, Huanhuan Qu, Chen Zhang, Chunying Xiao, Bingyu Pang, Meng Fu, Hongjiang Qiao, Shuai Shao, Erle Dang, Gang Wang
Hui Fang, Shengxian Shen, Kang Li, Tianyu Cao, Bing Wang, Haijun Miao, Ke Xue, Yaxing Bai, Liang Li, Xia Li, Pei Qiao, Jieyu Zhang, Huanhuan Qu, Chen Zhang, Chunying Xiao, Bingyu Pang, Meng Fu, Hongjiang Qiao, Shuai Shao, Erle Dang, Gang Wang
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Research Article Autoimmunity Dermatology

CD20+ T follicular helper–like cells drive antigen-specific autoimmunity in bullous pemphigoid

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Abstract

CD20+ T cells are increasingly recognized as drivers of autoimmune and inflammatory diseases. However, their origin, development, and specific role in autoimmune skin diseases remain poorly understood. In this study, we observed an expansion of CD20+ T cells in the peripheral blood and skin lesions of patients with bullous pemphigoid (BP), which correlated with the levels of pathogenic autoantibodies and disease severity. Compared with CD20– T cells, CD20+ T cells exhibited enhanced metabolic and pro-inflammatory activities. In particular, antigen-specific BP180-NC16A–reactive T cells were enriched within the CD4+CD20+ subset. In both patients with BP and BP180-immunized mice, CD4+CD20+ T cells exhibited an antigen-specific T follicular helper–like phenotype, facilitating antibody production and B cell differentiation, whereas CD8+CD20+ T cells displayed cytotoxic and pro-inflammatory features. Mechanistically, we found that expression of the CD20-encoding gene MS4A1 in T cells was regulated by transcription factor PAX5 in a DNA methylation–dependent manner. Therefore, our study elucidates the regulatory mechanisms governing CD20+ T cells and highlights their important role in the pathogenesis of BP.

Authors

Hui Fang, Shengxian Shen, Kang Li, Tianyu Cao, Bing Wang, Haijun Miao, Ke Xue, Yaxing Bai, Liang Li, Xia Li, Pei Qiao, Jieyu Zhang, Huanhuan Qu, Chen Zhang, Chunying Xiao, Bingyu Pang, Meng Fu, Hongjiang Qiao, Shuai Shao, Erle Dang, Gang Wang

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Figure 5

CD20+ T cells are increased in BP180-immunized mice and promote B cell differentiation and antibody production.

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CD20+ T cells are increased in BP180-immunized mice and promote B cell d...
(A) Serum anti-BP180 antibody titers in control and BP180-immunized mice at week 4, as measured by ELISA (n = 8). (B) Representative direct immunofluorescence images showing IgG and C3 deposition (green) in back skin sections. Scale bar = 100 μm. (C) Frequencies of CD4+CD20+ T cells in the spleen, lymph nodes, and peripheral blood of control and BP180-immunized mice (n = 6). (D) Frequencies of CXCR5+PD-1+ cells among CD4+CD20+ and CD4+CD20– T cells in the spleen, lymph nodes, and peripheral blood of control and BP180-immunized mice (n = 5). (E) MFI of IL-21 in CD4+CD20+ or CD4+CD20– T cells in the spleen of control and BP180-immunized mice (n = 5). (F) Anti-BP180 antibody titers in cell culture supernatants from each group were measured by ELISA (n = 5). (G) Serum anti-BP180 antibody titers in each group of Rag1–/– mice that received adoptive transfer of B cells along with T cell subsets (or B cells alone as control), measured by ELISA (n = 5). (H) Frequencies of GL7+Fas+ germinal center (GC) B cells among B220+ B cells and IgD–CD138+ plasma cells in Rag1–/– recipient mice (n = 5). (I) Frequencies of CXCR5+PD-1+ T cells within CD4+ T cells from negative control–knockout (NC-KO) and MS4A1-knockout (MS4A1-KO) T cells (n = 4). (J) MFI of IL-21 in CD4+ T cells from control and MS4A1-KO T cells (n = 4). All data are presented as the mean ± SD. An unpaired 2-tailed Student’s t test was used for A, C, I, and J; 1-way ANOVA with Tukey’s post hoc test was used for F–H; and 2-way ANOVA with Tukey’s post hoc test was used for D and E. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.

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

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