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10.1016/j.immuni.2016.04.013

http://scihub22266oqcxt.onion/10.1016/j.immuni.2016.04.013
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suck abstract from ncbi


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pmid27261277
      Immunity 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.
  • |*Autoimmunity [MESH]
  • |*Immunity, Humoral [MESH]
  • |Animals [MESH]
  • |B-Lymphocytes/*immunology [MESH]
  • |Basic-Leucine Zipper Transcription Factors/genetics/metabolism [MESH]
  • |Calcium Release Activated Calcium Channels/metabolism [MESH]
  • |Calcium Signaling [MESH]
  • |Cells, Cultured [MESH]
  • |Germinal Center/*immunology [MESH]
  • |Interferon Regulatory Factors/genetics/metabolism [MESH]
  • |Mice [MESH]
  • |Mice, Inbred C57BL [MESH]
  • |Mice, Knockout [MESH]
  • |NFATC Transcription Factors/metabolism [MESH]
  • |ORAI1 Protein/metabolism [MESH]
  • |Proto-Oncogene Proteins c-bcl-6/genetics/metabolism [MESH]
  • |Stromal Interaction Molecule 1/genetics/*metabolism [MESH]
  • |Stromal Interaction Molecule 2/genetics/*metabolism [MESH]


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