Mizoguchi C, Uehara S, Akira S, Takatsu K
Department of Immunology, Institute of Medical Science, University of Tokyo, Japan.
J Immunol. 1999 Mar 1;162(5):2812-9.
Mouse B cells express CD38, whose ligation by anti-CD38 Ab induces their proliferation and protection from apoptosis. We previously showed that stimulation of mouse splenic B cells with IL-5 together with CS/2, an anti-mouse CD38 mAb, induces production of IgG1 and IgM. Here we examined the role of IL-5 and CS/2 in the expression of germline gamma1 transcripts and the generation of reciprocal products forming DNA circles as byproducts of mu-gamma1 switch recombination. By itself, CS/2 induced significant expression of germline gamma1 transcripts in splenic naive B cells, whereas IL-5 neither induced nor enhanced germline gamma1 expression. Increased cellular content of reciprocal product, which is characteristic of mu-gamma1 recombination, was not observed after culturing B cells with CS/2, but increased reciprocal product, along with high levels of lgG1 secretion, was found when B cells were cultured with CS/2 plus IL-5. Although IL-4 did not, by itself, induce mu-gamma1 recombination in B cells stimulated with CS/2, in conjunction with CS/2 plus IL-5, IL-4 dramatically enhanced sterile gamma1 transcription and IgG1 production. These results demonstrate that CD38 ligation induces only germline gamma1 transcription and that IL-5 promotes both mu-gamma1 switch recombination and lgG1 secretion in an IL-4-independent manner.
小鼠B细胞表达CD38，抗CD38抗体与CD38结合可诱导其增殖并保护其免于凋亡。我们之前发现，用白细胞介素-5（IL-5）与抗小鼠CD38单克隆抗体CS/2共同刺激小鼠脾脏B细胞，可诱导IgG1和IgM的产生。在此，我们研究了IL-5和CS/2在种系γ1转录本表达以及作为μ-γ1类别转换重组副产物形成DNA环的相互产物生成中的作用。单独使用时，CS/2可诱导脾脏幼稚B细胞中种系γ1转录本的显著表达，而IL-5既不诱导也不增强种系γ1的表达。在用CS/2培养B细胞后，未观察到相互产物细胞含量增加，这是μ-γ1重组的特征，但当用CS/2加IL-5培养B细胞时，发现相互产物增加，同时伴有高水平的IgG1分泌。尽管IL-4本身不会在CS/2刺激的B细胞中诱导μ-γ1重组，但与CS/2加IL-5联合使用时，IL-4可显著增强无菌γ1转录和IgG1产生。这些结果表明，CD38结合仅诱导种系γ1转录，而IL-5以不依赖IL-4的方式促进μ-γ1类别转换重组和IgG1分泌。
