Wysocki L J, Creadon G, Lehmann K R, Cambier J C
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206.
Immunology. 1992 Jan;75(1):116-21.
Somatic mutations that are acquired by antibody V genes of antigen-stimulated B cells ultimately provide the clonal diversity from which memory B cells are selected during immune responses to T-cell-dependent antigens. Somatic mutations apparently are not acquired when B cells are stimulated by mitogens nor when they participate in immune responses to T-cell-independent antigens. Since the basis of T-cell-dependent humoral immunity is T-cell recognition of processed antigen in the context of class II major histocompatibility glycoproteins (Ia) on the B-cell surface, we sought to determine whether the ligation of Ia on B cells induces somatic mutation. B cells were stimulated in vitro by a procedure in which their proliferation was dependent upon ligation of surface Ia with antibody. Sequences of hybridoma V genes derived from these B cells revealed no somatic mutations despite prolonged stimulation in vitro and the induction of immunoglobulin secretion and switching to isotypes characteristic of T cell-dependent humoral immunity. We infer that Ia-mediated signalling and isotype switching are not causally related to somatic mutation. The avenue of differentiation that leads to somatic mutation in memory B cells is apparently separable from that leading to proliferation, immunoglobulin secretion and switching.
抗原刺激的B细胞的抗体V基因获得的体细胞突变最终提供了克隆多样性，在对T细胞依赖性抗原的免疫反应中，记忆B细胞就是从这种克隆多样性中被选择出来的。当B细胞受到有丝分裂原刺激时，或者当它们参与对T细胞非依赖性抗原的免疫反应时，显然不会获得体细胞突变。由于T细胞依赖性体液免疫的基础是T细胞在B细胞表面II类主要组织相容性糖蛋白（Ia）的背景下识别加工后的抗原，我们试图确定B细胞上Ia的连接是否会诱导体细胞突变。通过一种体外刺激B细胞的方法，其增殖依赖于表面Ia与抗体的连接。尽管在体外进行了长时间刺激，并诱导了免疫球蛋白分泌以及向T细胞依赖性体液免疫特征性同种型的转换，但从这些B细胞衍生的杂交瘤V基因序列未显示体细胞突变。我们推断，Ia介导的信号传导和同种型转换与体细胞突变没有因果关系。导致记忆B细胞体细胞突变的分化途径显然与导致增殖、免疫球蛋白分泌和转换的途径是分开的。
