Eyerman M C, Zhang X, Wysocki L J
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA.
J Immunol. 1996 Aug 1;157(3):1037-46.
The capacity of B cells to self-present their Ab variable regions in the context of class II MHC structures suggests a potential regulatory problem. If T cells were able to recognize self-presented Ab, then T cell help might be delivered to B cells independently of a foreign carrier epitope, resulting in a chronic state of unregulated Ab synthesis. For this reason, we have proposed that T cells normally attain a state of tolerance to Ab V region diversity. Here, we tested this idea by performing direct immunizations with unmutated isologous mAb. We also identified and analyzed epitopes recognized by class II MHC-restricted T cell hybridomas that were originally generated against two physiologically mutated isologous mAb. Our results indicate that the class II MHC-restricted T cell repertoire is tolerant of germ-line-encoded Ab diversity and that the physiologic somatic hypermutation process creates immunogenic epitopes in Ab V regions, in some cases by producing class II MHC-binding peptides. In agreement with these findings, we found that germ-line-encoded Ab V regions are presented by endogenous splenic APC at a level that is physiologically significant.
B细胞在II类MHC结构的背景下自我呈递其抗体可变区的能力提示了一个潜在的调控问题。如果T细胞能够识别自我呈递的抗体，那么T细胞的辅助可能会独立于外来载体表位而传递给B细胞，导致抗体合成不受调控的慢性状态。因此，我们提出T细胞通常会达到对抗体V区多样性的耐受状态。在此，我们通过用未突变的同源单克隆抗体进行直接免疫来验证这一想法。我们还鉴定并分析了最初针对两种生理突变的同源单克隆抗体产生的II类MHC限制性T细胞杂交瘤所识别的表位。我们的结果表明，II类MHC限制性T细胞库耐受种系编码的抗体多样性，并且生理上的体细胞超突变过程在抗体V区产生免疫原性表位，在某些情况下是通过产生II类MHC结合肽来实现的。与这些发现一致，我们发现种系编码的抗体V区由内源性脾脏抗原呈递细胞以具有生理意义的水平呈递。
