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

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

Research output: Contribution to journalArticlepeer-review

181 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)703-714
Number of pages12
JournalImmunity
Volume34
Issue number5
DOIs
Publication statusPublished - May 27 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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