deficiency causes spontaneous autoimmunity by breaking B cell tolerance


Zeng J, Aryal RP, Stavenhagen K, Luo C, Liu R, Wang X, Chen J, Li H, Matsumoto Y, Wang Y, et al. deficiency causes spontaneous autoimmunity by breaking B cell tolerance. Sci Adv. 2021;7 (41) :eabg9118.

Date Published:

2021 Oct 08


Factors regulating the induction and development of B cell–mediated autoimmunity are not well understood. Here, we report that targeted deletion in murine B cells of X-linked Cosmc, encoding the chaperone required for expression of core 1 O-glycans, causes the spontaneous development of autoimmune pathologies due to a breakdown of B cell tolerance. BC-CosmcKO mice display multiple phenotypic abnormalities, including severe weight loss, ocular manifestations, lymphadenopathy, and increased female-associated mortality. Disruption of B cell tolerance in BC-CosmcKO mice is manifested as elevated self-reactive IgM and IgG autoantibodies. Cosmc-deficient B cells exhibit enhanced basal activation and responsiveness to stimuli. There is also an elevated frequency of spontaneous germinal center B cells in BC-CosmcKO mice. Mechanistically, loss of Cosmc confers enhanced B cell receptor (BCR) signaling through diminished BCR internalization. The results demonstrate that Cosmc, through control of core 1 O-glycans, is a previously unidentified immune checkpoint gene in maintaining B cell tolerance.
Last updated on 06/07/2022