Snapper C M, Yamada H, Smoot D, Sneed R, Lees A, Mond J J
Dept. of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
J Immunol. 1993 Apr 1;150(7):2737-45.
We have previously demonstrated that activation of murine B cells by dextran-conjugated anti-IgD antibodies may serve as a polyclonal, in vitro model system for studying immune responses to T cell-independent type 2 (TI-2) Ag, as exemplified by the bacterial polysaccharides. Because in vivo Ig responses to TI-2 Ag are mediated primarily by B cells resident in the splenic marginal zone, we wished to determine whether this reflected an intrinsic difference in the responsiveness of marginal zone B cells (MZB) compared with follicular B cells (FB) to this class of Ag. In this report we demonstrate that highly purified MZB, isolated by electronic cell sorting, exhibit a lower proliferative response in vitro in response to unconjugated anti-Ig antibody as well as to dextran- or Sepharose-conjugated anti-IgM or anti-IgD antibodies, whereas they proliferate equal to or better than FB when stimulated by other B cell mitogens including LPS, Salmonella typhimurium mitogen, or anti-CD3-activated CD4+ Th2 cell clone. Despite the different proliferative responses of MZB and FB induced by anti-Ig, Ag receptor cross-linkage stimulates comparable increases in intracellular free calcium concentrations in both of these B cell populations. Furthermore, MZB secrete Ig and undergo Ig isotype switching to a comparable degree, relative to FB, in response to both T cell-dependent and T cell-independent stimuli. This suggests that the compartmentalization of TI-2 responses to the splenic marginal zone rather than the follicular zone reflects something other than the intrinsic responsiveness of the B cells from these two sites.
我们之前已经证明，用葡聚糖偶联的抗IgD抗体激活小鼠B细胞，可作为一种多克隆体外模型系统，用于研究对2型非T细胞依赖性（TI-2）抗原的免疫反应，细菌多糖就是这类抗原的例子。由于体内对TI-2抗原的Ig反应主要由脾脏边缘区的B细胞介导，我们希望确定这是否反映了边缘区B细胞（MZB）与滤泡B细胞（FB）对这类抗原反应性的内在差异。在本报告中，我们证明，通过电子细胞分选分离得到的高度纯化的MZB，在体外对未偶联的抗Ig抗体以及葡聚糖或琼脂糖偶联的抗IgM或抗IgD抗体的反应中，增殖反应较低，而当受到其他B细胞有丝分裂原刺激时，包括脂多糖、鼠伤寒沙门氏菌有丝分裂原或抗CD3激活的CD4+ Th2细胞克隆，它们的增殖能力与FB相当或更强。尽管抗Ig诱导的MZB和FB的增殖反应不同，但抗原受体交联在这两种B细胞群体中均刺激细胞内游离钙浓度出现相当程度的增加。此外，相对于FB，MZB在对T细胞依赖性和非T细胞依赖性刺激的反应中，分泌Ig并进行Ig同种型转换的程度相当。这表明，TI-2反应在脾脏边缘区而非滤泡区的分隔反映的不是这两个部位B细胞的内在反应性。
