Antigen-presenting autoreactive B cells activate regulatory T cells and suppress autoimmune arthritis in mice
Mike Aoun, Ana Coelho, Alexander Krämer, Amit Saxena, Pierre Sabatier, Christian M. Beusch, Erik Lönnblom, Manman Geng, Nhu‐Nguyen Do, Zhongwei Xu, Jingdian Zhang, Yibo He, Laura Romero‐Castillo, Hassan Abolhassani, Bingze Xu, Johan Viljanen, Joanna Rorbach, Gonzalo Fernandez Lahore, Inger Gjertsson, Alf Kastbom, Christopher Sjöwall, Jan Kihlberg, Roman A. Zubarev, Harald Burkhardt, Rikard Holmdahl
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 naïve B cells tolerize infiltrating T cells against self-antigens to impede the development of tissue-specific autoimmune inflammation.