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The Calcium Sensors STIM1 and STIM2 Control B Cell Regulatory Function through Interleukin-10 Production

2011; Cell Press; Volume: 34; Issue: 5 Linguagem: Inglês

10.1016/j.immuni.2011.03.016

1097-4180

Masanori Matsumoto, Yoko Fujii, Akemi Baba, Masaki Hikida, Tomohiro Kurosaki, Yoshihiro Baba,

Toxin Mechanisms and Immunotoxins

A chief Ca2+ entry pathway in immune cells is store-operated Ca2+ (SOC) influx, which is triggered by depletion of Ca2+ from the endoplasmic reticulum (ER). However, its physiological role in B cells remains elusive. Here, we show that ER calcium sensors STIM1- and STIM2-induced SOC influx is critical for B cell regulatory function. B cell-specific deletion of STIM1 and STIM2 in mice caused a profound defect in B cell receptor (BCR)-induced SOC influx and proliferation. However, B cell development and antibody responses were unaffected. Remarkably, B cells lacking both STIM proteins failed to produce the anti-inflammatory cytokine IL-10 because of defective activation of nuclear factor of activated T cells (NFAT) after BCR stimulation. This resulted in exacerbation of experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. Our data establish STIM-dependent SOC influx as a key signal for B cell regulatory function required to limit autoimmunity.