The survival and function of IL-10-producing regulatory B cells are negatively controlled by SLAMF5

B cells have essential functions in multiple sclerosis and in its mouse model, experimental autoimmune encephalomyelitis, both as drivers and suppressors of the disease. The suppressive effects are driven by a regulatory B cell (Breg) population that functions, primarily but not exclusively, via the production of IL-10. However, the mechanisms modulating IL-10-producing Breg abundance are poorly understood. Here we identify SLAMF5 for controlling IL-10(+) Breg maintenance and function. In EAE, the deficiency of SLAMF5 in B cells causes accumulation of IL10(+) Bregs in the central nervous system and periphery. Blocking SLAMF5 in vitro induces both human and mouse IL-10-producing Breg cells and increases their survival with a concomitant increase of a transcription factor, c-Maf. Finally, in vivo SLAMF5 blocking in EAE elevates IL-10(+) Breg levels and ameliorates disease severity. Our results suggest that SLAMF5 is a negative moderator of IL-10(+) Breg cells, and may serve as a therapeutic target in MS and other autoimmune diseases. Regulatory B (Breg) cells suppress excessive inflammation primary via the production of interleukin 10 (IL-10). Here the authors show that the function and homeostasis of mouse and human IL-10(+) Breg cells are negatively regulated by the cell surface receptor, SLAMF5, to impact experimental autoimmunity, thereby hinting SLAMF5 as a potential target for immunotherapy.

Automated summary

Regulatory B (Breg) cells suppress excessive inflammation primary via the production of interleukin 10 (IL-10). Here the authors show that the function and homeostasis of mouse and human IL-10(+) Breg cells are negatively regulated by the cell surface receptor, SLAMF5, to impact experimental autoimmunity, thereby hinting SLAMF5 as a potential target for immunotherapy.