Bishop G A, Ramirez L M, Waldschmidt T J
Department of Microbiology, University of Iowa, Iowa City 52242.
Int Immunol. 1994 Jul;6(7):1049-59. doi: 10.1093/intimm/6.7.1049.
B cells of mouse and human can be divided into distinct subpopulations, differing in distribution and phenotype. It is not known, however, whether B cell subsets respond similarly to signals mediated by cognate interactions with T cells, such as ligation of the B cell class II MHC molecule. Mouse splenic B cells proliferate in response to a combination of non-mitogenic anti-mu mAb, IL-4 and class II MHC-specific mAbs. In order to assess the response of B cell subpopulations to these signals, B cells were separated on the basis of CD23 expression. Previous studies have shown that CD23 expression is useful in distinguishing marginal zone from follicular B cells and peritoneal B1 from B2 B cells. B cells of both subsets responded to the combination of signals, but CD23- B cells showed a higher response. Splenic B cells were also purified from several strains of autoimmune mice, of interest because their disease features expansion of CD23- B cells and autoantibody production. While normal B cells showed no response to non-mitogenic anti-mu mAb alone, B cells from autoimmune mice showed a marked decrease in proliferation. Addition of IL-4 plus class II-specific mAbs restored increased proliferation. Again, responses were higher in CD23- than in CD23+ B cells. These findings suggest that CD23- B cells are especially responsive to signals delivered through class II and the IL-4 receptor. These signals may allow preferential rescue of CD23-B cells from antigen-mediated tolerance and result in their hyperexpansion in response to autoreactive T cells.
小鼠和人类的B细胞可分为不同的亚群，其分布和表型有所不同。然而，尚不清楚B细胞亚群对与T细胞同源相互作用介导的信号（如B细胞II类MHC分子的连接）的反应是否相似。小鼠脾B细胞在非促有丝分裂抗μ单克隆抗体、IL-4和II类MHC特异性单克隆抗体的联合作用下增殖。为了评估B细胞亚群对这些信号的反应，根据CD23表达对B细胞进行了分离。先前的研究表明，CD23表达有助于区分边缘区B细胞与滤泡B细胞，以及腹膜B1细胞与B2 B细胞。两个亚群的B细胞都对信号组合有反应，但CD23阴性B细胞的反应更高。还从几种自身免疫小鼠品系中纯化了脾B细胞，这些小鼠之所以受到关注，是因为它们的疾病特征是CD23阴性B细胞扩增和自身抗体产生。虽然正常B细胞对单独的非促有丝分裂抗μ单克隆抗体无反应，但自身免疫小鼠的B细胞增殖明显减少。添加IL-4和II类特异性单克隆抗体可恢复增殖增加。同样，CD23阴性B细胞的反应高于CD23阳性B细胞。这些发现表明，CD23阴性B细胞对通过II类分子和IL-4受体传递的信号特别敏感。这些信号可能使CD23阴性B细胞优先从抗原介导的耐受中被挽救出来，并导致它们在对自身反应性T细胞的反应中过度扩增。
