Koizumi T, Ochi Y, Kobayashi S, Nakanishi M, Tokuhisa T
Department of Immunology, ICMR, Kobe University School of Medicine, Japan.
Cell Immunol. 1994 May;155(2):384-93. doi: 10.1006/cimm.1994.1131.
B cell activation by surface immunoglobulin (sIg) cross-linking is accompanied by transient expression of the c-fos protooncogene. This expression is strictly controlled in the B cells. To investigate a biological implication of the c-fos expression in the process of B cell activation by sIg cross-linking, we examined the proliferation of splenic B cells from H2-c-fos transgenic mice. Constitutive expression of the c-fos gene perturbs de novo synthesis of RNA and DNA in the B cells stimulated with anti-IgM antibody. Early events of signal transduction such as an increase in intracellular free calcium level and an induction of the endogenous immediate early genes (c-fos and c-myc) were apparently intact in those B cells. When the sIg stimulation of B cells was mimicked by the costimulation with 12-O-tetradecanoylphorbol 13-acetate and ionomycin, H2-c-fos B cells required higher concentrations of ionomycin for the optimal proliferative responses, suggesting that calcium-dependent signal transduction pathways are disturbed in those B cells. These results demonstrate a novel regulatory effect of c-fos protein on the proliferation of B cells mediated by sIg cross-linking.
通过表面免疫球蛋白（sIg）交联激活B细胞伴随着原癌基因c-fos的瞬时表达。这种表达在B细胞中受到严格控制。为了研究c-fos表达在sIg交联激活B细胞过程中的生物学意义，我们检测了H2-c-fos转基因小鼠脾B细胞的增殖情况。c-fos基因的组成性表达干扰了用抗IgM抗体刺激的B细胞中RNA和DNA的从头合成。在这些B细胞中，信号转导的早期事件，如细胞内游离钙水平的升高和内源性即刻早期基因（c-fos和c-myc）的诱导，显然是完整的。当用12-O-十四酰佛波醇-13-乙酸酯和离子霉素共刺激模拟B细胞的sIg刺激时，H2-c-fos B细胞需要更高浓度的离子霉素才能产生最佳增殖反应，这表明这些B细胞中钙依赖性信号转导途径受到干扰。这些结果证明了c-fos蛋白对sIg交联介导的B细胞增殖具有新的调节作用。
