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          Institute: MPI für biophysikalische Chemie     Collection: Abteilungsunabhängige Arbeitsgruppen     Display Documents

ID: 270903.0, MPI für biophysikalische Chemie / Abteilungsunabhängige Arbeitsgruppen
Regulation of B-cell survival by BAFF-dependent PKCdelta-mediated nuclear signalling.
Authors:Mecklenbraeuker, I.; Kalled, S. L.; Leitges, M.; Mackay, F.; Tarakhovsky, A.
Date of Publication (YYYY-MM-DD):2004-09-23
Title of Journal:Nature
Issue / Number:7007
Start Page:456
End Page:461
Review Status:Peer-review
Audience:Experts Only
Abstract / Description:Approximately 65% of B cells generated in human bone marrow are potentially harmful autoreactive B cells. Most of these cells are clonally deleted in the bone marrow, while those autoreactive B cells that escape to the periphery are anergized or perish before becoming mature B cells. Escape of self-reactive B cells from tolerance permits production of pathogenic auto-antibodies; recent studies suggest that extended B lymphocyte survival is a cause of autoimmune disease in mice and humans. Here we report a mechanism for the regulation of peripheral B-cell survival by serine/threonine protein kinase Cdelta (PKCdelta): spontaneous death of resting B cells is regulated by nuclear localization of PKCdelta that contributes to phosphorylation of histone H2B at serine 14 (S14-H2B). We show that treatment of B cells with the potent B-cell survival factor BAFF ('B-cell-activating factor belonging to the TNF family') prevents nuclear accumulation of PKCdelta. Our data suggest the existence of a previously unknown BAFF-induced and PKCdelta-mediated nuclear signalling pathway which regulates B-cell survival.
Free Keywords:Animals; B-Lymphocytes/cytology/enzymology/metabolism; Cell Death; Cell Nucleus/enzymology/metabolism; Cell Survival; Cells, Cultured; Fibroblasts; Membrane Proteins/metabolism; Mice; Phosphorylation; Protein Kinase C/deficiency/genetics/metabolism; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Signal Transduction; Tumor Necrosis Factor-alpha/metabolism
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für biophysikalische Chemie/AG Leitges
MPI für biophysikalische Chemie/Abt. Eichele
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