Publications Search

Search for publications by author
Search for publications by abstract keyword(s)

Regulation of B-cell survival by BAFF-dependent PKCdelta-mediated nuclear signalling


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.

Type Journal
ISBN 1476-4687 (Electronic)
Authors Mecklenbrauker, I.;Kalled, S. L.;Leitges, M.;Mackay, F.;Tarakhovsky, A. :
Publisher Name NATURE
Published Date 2004-01-01
Published Volume 431
Published Issue 7007
Published Pages 456-61
Status Published in-print
URL link to publisher's version