Antigen-presenting autoreactive B cells activate regulatory T cells and suppress autoimmune arthritis in mice.

Aoun M, Coelho A, Krämer A, Saxena A, Sabatier P, Beusch CM, Lönnblom E, Geng M, Do NN, Xu Z, Zhang J, He Y, Romero Castillo L, Abolhassani H, Xu B, Viljanen J, Rorbach J, Fernandez Lahore G, Gjertsson I, Kastbom A, Sjöwall C, Kihlberg J, Zubarev RA, Burkhardt H, Holmdahl R

J. Exp. Med. 220 (11) - [2023-11-06; online 2023-09-11]

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.

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PubMed 37695523

DOI 10.1084/jem.20230101

Crossref 10.1084/jem.20230101

pmc: PMC10494526
pii: 276247