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2016 ; 44
(6
): 1350-64
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Store-Operated Ca(2+) Entry in Follicular T Cells Controls Humoral Immune
Responses and Autoimmunity
#MMPMID27261277
Vaeth M
; Eckstein M
; Shaw PJ
; Kozhaya L
; Yang J
; Berberich-Siebelt F
; Clancy R
; Unutmaz D
; Feske S
Immunity
2016[Jun]; 44
(6
): 1350-64
PMID27261277
show ga
T follicular helper (Tfh) cells promote affinity maturation of B cells in
germinal centers (GCs), whereas T follicular regulatory (Tfr) cells limit the GC
reaction. Store-operated Ca(2+) entry (SOCE) through Ca(2+) release-activated
Ca(2+) (CRAC) channels mediated by STIM and ORAI proteins is a fundamental
signaling pathway in T lymphocytes. Conditional deletion of Stim1 and Stim2 genes
in T cells abolished SOCE and strongly reduced antibody-mediated immune responses
following viral infection caused by impaired differentiation and function of Tfh
cells. Conversely, aging Stim1Stim2-deficient mice developed humoral autoimmunity
with spontaneous autoantibody production due to abolished Tfr cell
differentiation in the presence of residual Tfh cells. Mechanistically, SOCE
controlled Tfr and Tfh cell differentiation through NFAT-mediated IRF4, BATF, and
Bcl-6 transcription-factor expression. SOCE had a dual role in controlling the GC
reaction by regulating both Tfh and Tfr cell differentiation, thus enabling
protective B cell responses and preventing humoral autoimmunity.