Apoptotic cell death induced by anti-IgM antibody and phorbol esters is inhibited by interleukin-4 in human B lymphoma cell line MBC-1.
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.
Komada
Y
Y
Department of Pediatrics, Mie University School of Medicine, Japan.
Zhang
X L
XL
Zhou
Y W
YW
Tanaka
S
S
Higashigawa
M
M
Ido
M
M
Sakurai
M
M
D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003429:Cross Reactions / Q000276:immunology; D004247:DNA / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D007072:Immunoglobulin D / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000276:immunology*; D015847:Interleukin-4 / Q000502:physiology*; D016393:Lymphoma, B-Cell; D011493:Protein Kinase C / Q000502:physiology
D007072:Immunoglobulin D; D007075:Immunoglobulin M; D015847:Interleukin-4; D004247:DNA; D011493:Protein Kinase C; D002118:Calcium