title: NFATc1 affects mouse splenic B cell function by controlling the calcineurin--NFAT signaling network.
abstract: By studying mice in which the Nfatc1 gene was inactivated in bone marrow, spleen, or germinal center B cells, we show that NFATc1 supports the proliferation and suppresses the activation-induced cell death of splenic B cells upon B cell receptor (BCR) stimulation. BCR triggering leads to expression of NFATc1/αA, a short isoform of NFATc1, in splenic B cells. NFATc1 ablation impaired Ig class switch to IgG3 induced by T cell-independent type II antigens, as well as IgG3(+) plasmablast formation. Mice bearing NFATc1(-/-) B cells harbor twofold more interleukin 10-producing B cells. NFATc1(-/-) B cells suppress the synthesis of interferon-γ by T cells in vitro, and these mice exhibit a mild clinical course of experimental autoimmune encephalomyelitis. In large part, the defective functions of NFATc1(-/-) B cells are caused by decreased BCR-induced Ca(2+) flux and calcineurin (Cn) activation. By affecting CD22, Rcan1, CnA, and NFATc1/αA expression, NFATc1 controls the Ca(2+)-dependent Cn-NFAT signaling network and, thereby, the fate of splenic B cells upon BCR stimulation.
authors.affiliation: Department of Molecular Pathology, University of Würzburg, D-97080 Würzburg, Germany.
authors.forename: Sankar
authors.initials: S
authors.lastname: Bhattacharyya
authors.forename: Jolly
authors.initials: J
authors.lastname: Deb
authors.forename: Amiya K
authors.initials: AK
authors.lastname: Patra
authors.forename: Duong Anh
authors.initials: DA
authors.lastname: Thuy Pham
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.forename: Martin
authors.initials: M
authors.lastname: Vaeth
authors.forename: Friederike
authors.initials: F
authors.lastname: Berberich-Siebelt
authors.forename: Stefan
authors.initials: S
authors.lastname: Klein-Hessling
authors.forename: Edward D
authors.initials: ED
authors.lastname: Lamperti
authors.forename: Kurt
authors.initials: K
authors.lastname: Reifenberg
authors.forename: Julia
authors.initials: J
authors.lastname: Jellusova
authors.forename: Astrid
authors.initials: A
authors.lastname: Schweizer
authors.forename: Lars
authors.initials: L
authors.lastname: Nitschke
authors.forename: Ellen
authors.initials: E
authors.lastname: Leich
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: Cornelia
authors.initials: C
authors.lastname: Brunner
authors.forename: Swen
authors.initials: S
authors.lastname: Engelmann
authors.forename: Ursula
authors.initials: U
authors.lastname: Bommhardt
authors.forename: Andris
authors.initials: A
authors.lastname: Avots
authors.forename: Martin R
authors.initials: MR
authors.lastname: Müller
authors.forename: Eisaku
authors.initials: E
authors.lastname: Kondo
authors.forename: Edgar
authors.initials: E
authors.lastname: Serfling
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D019703:Calcineurin / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D017578:Immunoglobulin Class Switching; D008213:Lymphocyte Activation; D051379:Mice; D050778:NFATC Transcription Factors / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013154:Spleen / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology
chemical_list: D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D011947:Receptors, Antigen, B-Cell; D019703:Calcineurin; D002118:Calcium