NFATc1 affects mouse splenic B cell function by controlling the calcineurin-NFAT signaling network

被引：91

作者：

Bhattacharyya, Sankar ^{[1
]}

Deb, Jolly ^{[1
]}

Patra, Amiya K. ^{[1
]}

Duong Anh Thuy Pham ^{[1
]}

Chen, Wen ^{[1
]}

Vaeth, Martin ^{[1
]}

Berberich-Siebelt, Friederike ^{[1
]}

Klein-Hessling, Stefan ^{[1
]}

Lamperti, Edward D. ^{[3
,4
]}

Reifenberg, Kurt ^{[5
]}

Jellusova, Julia ^{[6
]}

Schweizer, Astrid ^{[6
]}

Nitschke, Lars ^{[6
]}

Leich, Ellen ^{[2
]}

Rosenwald, Andreas ^{[2
]}

Brunner, Cornelia ^{[7
]}

Engelmann, Swen ^{[8
]}

Bommhardt, Ursula ^{[8
]}

Avots, Andris ^{[1
]}

Mueller, Martin R. ^{[3
,4
]}

Kondo, Eisaku ^{[9
]}

Serfling, Edgar ^{[1
]}

机构：

[1] Univ Wurzburg, Dept Mol Pathol, D-97080 Wurzburg, Germany

[2] Univ Wurzburg, Inst Pathol, D-97080 Wurzburg, Germany

[3] Immune Dis Inst, Boston, MA 02114 USA

[4] Harvard Univ, Sch Med, Boston, MA 02114 USA

[5] Johannes Gutenberg Univ Mainz, Cent Anim Facil, D-55101 Mainz, Germany

[6] Univ Erlangen Nurnberg, Dept Genet, D-91058 Erlangen, Germany

[7] Univ Ulm, Dept Physiol Chem, D-89081 Ulm, Germany

[8] Univ Magdeburg, Inst Med & Clin Immunol, D-39120 Magdeburg, Germany

[9] Okayama Univ, Dept Pathol, Grad Sch Med Dent & Pharmaceut Sci, Okayama 7008558, Japan

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2011年 / 208卷 / 04期

关键词：

TRANSCRIPTION FACTOR; T-CELLS; PHOSPHOLIPASE C-GAMMA-2; AUTOIMMUNE-DISEASES; NEGATIVE REGULATOR; DUAL ROLES; GENE; EXPRESSION; MICE; ACTIVATION;

D O I：

10.1084/jem.20100945

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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/alpha A, 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 IgG31(+) plasmablast formation. Mice bearing NFATc1(-/-) B cells harbor twofold more interleukin 10-producing B cells. NFATc1(-/-) B cells suppress the synthesis of interferon-gamma 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 Ca2+ flux and calcineurin (Cn) activation. By affecting CD22, Rcan1, CnA, and NFATc1/alpha A expression, NFATc1 controls the Ca2+-dependent Cn-NFAT signaling network and, thereby, the fate of splenic B cells upon BCR stimulation.

引用

页码：823 / 839

页数：17

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