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Updated: Mar 30, 2026

In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells
Published on: January 20, 2019
Regulation of B-cell survival by BAFF-dependent PKCdelta-mediated nuclear signalling
Ingrid Mecklenbräuker1, Susan L Kalled, Michael Leitges
1Laboratory of Lymphocyte Signaling, The Rockefeller University, New York, New York 10021, USA.
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 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.
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