期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 126, 期 1, 页码 282-287出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI83840
关键词
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资金
- National Institute of Allergy and Infectious Diseases (NIAID), NIH [AI061093, AI071087, AI082713, AI095848]
- Type 1 Diabetes TrialNet Pathway to Prevention Study Group
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [P01AI061093, R01AI071087, U19AI082713, R21AI095848] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [U01DK107014, U01DK061058, U01DK061010, U01DK085499, U01DK103266, U01DK103153, U01DK106984, U01DK085465, U01DK085476] Funding Source: NIH RePORTER
Type 1 diabetes (T1D) patients show abnormalities in early B cell tolerance checkpoints, resulting in the accumulation of large numbers of autoreactive B cells in their blood. Treatment with rituximab, an anti-CD20 mAb that depletes B cells, has been shown to preserve beta cell function in T1D patients and improve other autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. However, it remains largely unknown how anti-B cell therapy thwarts autoimmunity in these pathologies. Here, we analyzed the reactivity of Abs expressed by single, mature naive B cells from 4 patients with T1D before and 52 weeks after treatment to determine whether rituximab resets early B cell tolerance checkpoints. We found that anti-B cell therapy did not alter the frequencies of autoreactive and polyreactive B cells, which remained elevated in the blood of all patients after rituximab treatment. Moreover, the limited proliferative history of autoreactive B cells after treatment revealed that these clones were newly generated B cells and not self-reactive B cells that had escaped depletion and repopulated the periphery through homeostatic expansion. We conclude that anti-B cell therapy may provide a temporary dampening of autoimmune processes through B cell depletion. However, repletion with autoreactive B cells may explain the relapse that occurs in many autoimmune patients after anti-B cell therapy.
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