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

Lihi Radomir, Matthias P Kramer, Michal Perpinial, Nofar Schottlender, Stav Rabani, Keren David, Anna Wiener, Hadas Lewinsky, Shirly Becker-Herman, Rina Aharoni, Ron Milo, Claudia Mauri, Idit Shachar

Nature communications 2021 Mar 25

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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.

Citation

Lihi Radomir, Matthias P Kramer, Michal Perpinial, Nofar Schottlender, Stav Rabani, Keren David, Anna Wiener, Hadas Lewinsky, Shirly Becker-Herman, Rina Aharoni, Ron Milo, Claudia Mauri, Idit Shachar. The survival and function of IL-10-producing regulatory B cells are negatively controlled by SLAMF5. Nature communications. 2021 Mar 25;12(1):1893