Rohrer J W, Gershon R K, Lynch R G, Kemp J D
Department of Microbiology and Immunology, University of South Alabama College of Medicine, Mobile.
J Mol Cell Immunol. 1983;1(1):50-64.
The question of how many helper T cells are required for producing optimal antibody responses and what function each of the candidate helper cells performs are subjects of intense interest (and controversy) to the majority of immunologists. Our manuscript directly demonstrates for the first time that B cell clone growth and secretory differentiation are controlled by two distinct classes of helper T cells which can be discriminated from one another by profiles of their expressed cell surface alloantigens. There is a significant amount of inferential evidence that two types of helper T cells are required to interact with B cells and antigen in order to induce maximal antibody responses. In all reports, classical MHC-restricted, carrier-specific helper T cells (TH 1) had to interact with hapten-specific B cells via carrier-hapten bridges before the second helper cell (TH 2) could act. In contrast to the TH 1 cells, TH 2 cells have been reported neither to be MHC-restricted nor to require carrier-hapten bridges in their interaction with hapten-specific B cells. That certain isotype-, allotype-, or idiotype-expressing portions of the antigen-induced antibody response are preferentially enhanced in the presence of and depleted in the absence of the appropriate TH 2 cells has led to the suggestion that such TH 2 cells interact with B cells through receptors specific for determinants expressed on B cell surface immunoglobulin molecules. That TH 2 cells recognize autologous immunoglobulin determinants is also indirectly supported by their reported absence in appropriately immunized mice which were deficient in the relevant immunoglobulin during ontogeny [e.g. all TH 2 cells in anti-mu-treated mice; T15-specific TH 2 cells in (CBA/N X BALB/c)F1 male Xid mice which lack T15+ B cells]. It has been suggested that TH 2 cells recognize not only autologous immunoglobulin determinants but also "nominal" antigen since they have been reported to be dependent on antigen priming and reexposure to the priming antigen. However, to establish firmly that a TH 2 cell expresses receptors for both antigen and Ig determinants, one must isolate that helper cell by virtue of its receptor for one of these two moieties and show that the isolated cell has receptors for the other. We have done this, as well as showing that the Ig-recognizing, carrier-immune T cell selectively enhanced B cell secretory differentiation while having no effect on clonal expansion.(ABSTRACT TRUNCATED AT 400 WORDS)
产生最佳抗体反应需要多少辅助性T细胞,以及每个候选辅助性T细胞执行何种功能,这一问题是大多数免疫学家极为关注(且存在争议)的课题。我们的论文首次直接证明,B细胞克隆生长和分泌分化由两类不同的辅助性T细胞控制,这两类细胞可通过其表达的细胞表面同种异体抗原谱加以区分。有大量推断性证据表明,需要两种类型的辅助性T细胞与B细胞及抗原相互作用,才能诱导最大程度的抗体反应。在所有报告中,经典的MHC限制的、载体特异性辅助性T细胞(TH1)必须通过载体-半抗原桥与半抗原特异性B细胞相互作用,然后第二种辅助性T细胞(TH2)才能发挥作用。与TH1细胞不同,据报道TH2细胞在与半抗原特异性B细胞相互作用时既不受MHC限制,也不需要载体-半抗原桥。抗原诱导的抗体反应中某些表达同种型、同种异型或独特型的部分,在存在适当的TH2细胞时优先增强,而在没有TH2细胞时则减少,这表明此类TH2细胞通过对B细胞表面免疫球蛋白分子上表达的决定簇具有特异性的受体与B细胞相互作用。TH2细胞识别自身免疫球蛋白决定簇这一点也得到间接支持,据报道,在个体发育期间缺乏相关免疫球蛋白的适当免疫小鼠中不存在TH2细胞[例如,抗μ处理小鼠中的所有TH2细胞;(CBA/N×BALB/c)F1雄性Xid小鼠中缺乏T15+B细胞的T15特异性TH2细胞]。有人提出,TH2细胞不仅识别自身免疫球蛋白决定簇,还识别“名义”抗原,因为据报道它们依赖于抗原致敏和再次接触致敏抗原。然而,要确凿地证明TH2细胞表达针对抗原和Ig决定簇的受体,就必须根据其对这两种成分之一的受体分离出该辅助性细胞,并证明分离出的细胞具有针对另一种成分的受体。我们已经做到了这一点,同时还表明,识别Ig的、载体免疫的T细胞选择性增强B细胞分泌分化,而对克隆扩增没有影响。(摘要截短于400字)