Stevens T L, Bossie A, Sanders V M, Fernandez-Botran R, Coffman R L, Mosmann T R, Vitetta E S
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.
Nature. 1988 Jul 21;334(6179):255-8. doi: 10.1038/334255a0.
The regulation of the subclass of immunoglobulin secreted by B cells has been studied in vitro in polyclonal systems using mitogens, such as lipopolysaccharide (LPS), to bypass the requirement for cognate interaction between antigen-specific T and B cells. In these systems, interleukin-(IL)-4 induces the secretion of IgG1 (ref. 1) and IgE (ref. 2); IL-5 enhances the secretion of IgA, and interferon-gamma (IFN-gamma) enhances the secretion of IgG2a (ref. 5). Clones of murine TH cells can be divided into two subsets, TH1 and TH2 (ref. 6). Both subsets synthesize IL-3 and granulocyte-monocyte colony-stimulating factor (GM-CSF), but only TH1 clones produce IL-2, IFN-gamma, and lymphotoxin (LT) and TH2 clones produce IL-4 and IL-5 (ref. 7). We have examined the role of clones of antigen-specific TH1 and TH2 cells in the regulation of the subclasses of IgG antibody secreted by antigen-specific B cells. Our results show that both types of TH cells induce the secretion of IgM and IgG3, whereas clones of TH1 and TH2 cells specifically induce antigen-specific B cells to secrete IgG2a and IgG1, respectively. We also demonstrate that regulation of commitment to the secretion of a particular IgG isotype occurs in two distinct stages: cognate interaction between T and B cells and interaction between T-cell-derived lymphokines and B cells.
在体外多克隆系统中，利用丝裂原（如脂多糖，LPS）绕过抗原特异性T细胞和B细胞之间同源相互作用的需求，对B细胞分泌的免疫球蛋白亚类的调节进行了研究。在这些系统中，白细胞介素-（IL）-4诱导IgG1（参考文献1）和IgE（参考文献2）的分泌；IL-5增强IgA的分泌，而干扰素-γ（IFN-γ）增强IgG2a的分泌（参考文献5）。小鼠TH细胞克隆可分为两个亚群，TH1和TH2（参考文献6）。两个亚群都合成IL-3和粒细胞-单核细胞集落刺激因子（GM-CSF），但只有TH1克隆产生IL-2、IFN-γ和淋巴毒素（LT），而TH2克隆产生IL-4和IL-5（参考文献7）。我们研究了抗原特异性TH1和TH2细胞克隆在调节抗原特异性B细胞分泌的IgG抗体亚类中的作用。我们的结果表明，这两种类型的TH细胞都诱导IgM和IgG3的分泌，而TH1和TH2细胞克隆分别特异性地诱导抗原特异性B细胞分泌IgG2a和IgG1。我们还证明，对特定IgG同种型分泌的定向调节发生在两个不同阶段：T细胞和B细胞之间的同源相互作用以及T细胞衍生的淋巴因子与B细胞之间的相互作用。
