The calcium sensors STIM1 and STIM2 control B cell regulatory function through interleukin-10 production.
Immunity
; 34(5): 703-14, 2011 May 27.
Article
in En
| MEDLINE
| ID: mdl-21530328
ABSTRACT
A chief Ca(2+) entry pathway in immune cells is store-operated Ca(2+) (SOC) influx, which is triggered by depletion of Ca(2+) 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Membrane Glycoproteins
/
B-Lymphocytes
/
Calcium
/
Interleukin-10
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Immunity
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2011
Type:
Article
Affiliation country:
Japan