Apoptotic Cell Death Induced by Anti-IgM Antibody and Phorbol Esters Is Inhibited by Interleukin-4 in Human B Lymphoma Cell Line MBC-1

Abstract

The development of B cell tolerance is believed to involve negative signaling to B cells derived from the binding of antigen to the B cell surface immunoglobulin. B cell lines that receive negative signals may provide useful models for studying the mechanisms of B cell tolerance. We have established a human B lymphoma cell line, MBC-1, positive for both surface IgM and IgD. The growth of MBC-1 cells is inhibited by anti-IgM antibody but not by anti-IgD antibody. The rapid time course of MBC-1 cell death, the morphologic feature of dying cells, and DNA fragmentation indicate that surface IgM cross-linking induces apoptotic cell death. Interestingly, interleukin-4 (IL-4) could rescue MBC-1 cells from this apoptotic signal. BCL-2 protein is neither expressed nor induced in MBC-1 cells. The treatment of MBC-1 cells with IL-4 does not interfere with mobilization of Ca2+ or induce any phenotypical change. In addition, phorbol 12-myristate 13-acetate and phorbol 12, 13-dibutyrate also induced growth inhibition followed by apoptotic cell death in MBC-1 cells. IL-4 is able to protect MBC-1 cells from cell death, but not from growth inhibition induced by protein kinase C activators. The results collectively suggest that IL-4 could inhibit the transduction of apoptotic signal following the activation of protein kinase C in MBC-1 cells.