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- Title
Regulation of B-cell survival by BAFF-dependent PKCd-mediated nuclear signalling.
- Authors
Mecklenbräuker, Ingrid; Kalied, Susan L.; Leitges, Michael; Mackay, Fabienne; Tarakhovsky, Alexander
- Abstract
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 Cd(PKCd): spontaneous death of resting B cells is regulated by nuclear localization of PKCdthat 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 PKCd. Our data suggest the existence of a previously unknown BAFF-induced and PKCd-mediated nuclear signalling pathway which regulates B-cell survival.
- Subjects
CELLULAR control mechanisms; B cells; BONE marrow; PROTEIN kinase C; APOPTOSIS; IMMUNOGLOBULINS
- Publication
Nature, 2004, Vol 431, Issue 7007, p456
- ISSN
0028-0836
- Publication type
Article
- DOI
10.1038/nature02955