학술논문
Antigen-presenting autoreactive B cells activate regulatory T cells and suppress autoimmune arthritis in mice
Document Type
Author
Aoun, Mike; Coelho, Ana; Kraemer, Alexander; Saxena, Amit; Sabatier, Pierre; Beusch, Christian Michel; Loennblom, Erik; Geng, Manman; Do, Nhu-Nguyen; Xu, Zhongwei; Zhang, Jingdian; He, Yibo; Romero Castillo, Laura; Abolhassani, Hassan; Xu, Bingze; Viljanen, Johan; Rorbach, Joanna; Fernandez Lahore, Gonzalo; Gjertsson, Inger; Kastbom, Alf; Sjöwall, Christopher; Kihlberg, Jan; Zubarev, Roman A.; Burkhardt, Harald; Holmdahl, Rikard
Source
Journal of Experimental Medicine. 220(11)
Subject
Language
English
ISSN
0022-1007
1540-9538
1540-9538
Abstract
B cells undergo several rounds of selection to eliminate potentially pathogenic autoreactive clones, but in contrast to T cells, evidence of positive selection of autoreactive B cells remains moot. Using unique tetramers, we traced natural autoreactive B cells (C1-B) specific for a defined triple-helical epitope on collagen type-II (COL2), constituting a sizeable fraction of the physiological B cell repertoire in mice, rats, and humans. Adoptive transfer of C1-B suppressed arthritis independently of IL10, separating them from IL10-secreting regulatory B cells. Single-cell sequencing revealed an antigen processing and presentation signature, including induced expression of CD72 and CCR7 as surface markers. C1-B presented COL2 to T cells and induced the expansion of regulatory T cells in a contact-dependent manner. CD72 blockade impeded this effect suggesting a new downstream suppressor mechanism that regulates antigen-specific T cell tolerization. Thus, our results indicate that autoreactive antigen-specific naive B cells tolerize infiltrating T cells against self-antigens to impede the development of tissue-specific autoimmune inflammation.