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

Author

Listed:
  • Ingrid Mecklenbräuker

    (The Rockefeller University)

  • Susan L. Kalled

    (Biogen Idec, Inc.)

  • Michael Leitges

    (Max Planck Institute for Experimental Endocrinology)

  • Fabienne Mackay

    (St Vincent Hospital, Darlinghurst)

  • Alexander Tarakhovsky

    (The Rockefeller University)

Abstract

Approximately 65% of B cells generated in human bone marrow are potentially harmful autoreactive B cells1. 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 cells2,3,4,5. Escape of self-reactive B cells from tolerance permits production of pathogenic auto-antibodies6; recent studies suggest that extended B lymphocyte survival is a cause of autoimmune disease in mice and humans7. Here we report a mechanism for the regulation of peripheral B-cell survival by serine/threonine protein kinase Cδ (PKCδ): spontaneous death of resting B cells is regulated by nuclear localization of PKCδ 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 PKCδ. Our data suggest the existence of a previously unknown BAFF-induced and PKCδ-mediated nuclear signalling pathway which regulates B-cell survival.

Suggested Citation

  • Ingrid Mecklenbräuker & Susan L. Kalled & Michael Leitges & Fabienne Mackay & Alexander Tarakhovsky, 2004. "Regulation of B-cell survival by BAFF-dependent PKCδ-mediated nuclear signalling," Nature, Nature, vol. 431(7007), pages 456-461, September.
    • Handle: RePEc:nat:nature:v:431:y:2004:i:7007:d:10.1038_nature02955
    DOI: 10.1038/nature02955
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