Komada Y, Zhang X L, Zhou Y W, Tanaka S, Higashigawa M, Ido M, Sakurai M
Department of Pediatrics, Mie University School of Medicine, Japan.
Cell Immunol. 1994 Dec;159(2):280-93. doi: 10.1006/cimm.1994.1314.
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.
B细胞耐受性的发展被认为涉及抗原与B细胞表面免疫球蛋白结合后向B细胞发出的负信号。接收负信号的B细胞系可能为研究B细胞耐受性机制提供有用的模型。我们建立了一种人B淋巴瘤细胞系MBC-1，其表面IgM和IgD均呈阳性。MBC-1细胞的生长受到抗IgM抗体的抑制，但不受抗IgD抗体的抑制。MBC-1细胞死亡的快速时间进程、死亡细胞的形态特征以及DNA片段化表明，表面IgM交联诱导凋亡性细胞死亡。有趣的是，白细胞介素-4（IL-4）可以使MBC-1细胞从这种凋亡信号中获救。BCL-2蛋白在MBC-1细胞中既不表达也不被诱导。用IL-4处理MBC-1细胞不会干扰Ca2+的动员或诱导任何表型变化。此外，佛波醇12-肉豆蔻酸酯13-乙酸酯和佛波醇12,13-二丁酸酯也诱导MBC-1细胞生长抑制，随后发生凋亡性细胞死亡。IL-4能够保护MBC-1细胞免于细胞死亡，但不能使其免受蛋白激酶C激活剂诱导的生长抑制。这些结果共同表明，IL-4可以抑制MBC-1细胞中蛋白激酶C激活后凋亡信号的转导。
