| First Author | Mecklenbräuker I | Year | 2004 |
| Journal | Nature | Volume | 431 |
| Issue | 7007 | Pages | 456-61 |
| PubMed ID | 15361883 | Mgi Jnum | J:92667 |
| Mgi Id | MGI:3054281 | Doi | 10.1038/nature02955 |
| Citation | Mecklenbrauker I, et al. (2004) Regulation of B-cell survival by BAFF-dependent PKCdelta-mediated nuclear signalling. Nature 431(7007):456-61 |
| abstractText | 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. |
