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 journalArticle

160 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

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Regulatory B-Lymphocytes
Interleukin-10
B-Lymphocytes
Calcium
Endoplasmic Reticulum
NFATC Transcription Factors
Autoimmune Experimental Encephalomyelitis
Autoimmunity
Multiple Sclerosis
Antibody Formation
Anti-Inflammatory Agents
Cytokines

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

The Calcium Sensors STIM1 and STIM2 Control B Cell Regulatory Function through Interleukin-10 Production. / Matsumoto, Masanori; Fujii, Yoko; Baba, Akemi; Hikida, Masaki; Kurosaki, Tomohiro; Baba, Yoshihiro.

In: Immunity, Vol. 34, No. 5, 27.05.2011, p. 703-714.

Research output: Contribution to journalArticle

Matsumoto, Masanori ; Fujii, Yoko ; Baba, Akemi ; Hikida, Masaki ; Kurosaki, Tomohiro ; Baba, Yoshihiro. / The Calcium Sensors STIM1 and STIM2 Control B Cell Regulatory Function through Interleukin-10 Production. In: Immunity. 2011 ; Vol. 34, No. 5. pp. 703-714.
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