Mo J A, Holmdahl R
Department of Cellular and Molecular Biology, Lund University, Sweden.
J Immunol. 1996 Sep 15;157(6):2440-8.
Collagen-induced arthritis is an autoimmune model disease induced in the DBA/1 mouse immunized with type II collagen (CII). Both T and B cells play a critical role for the induction of arthritis. Draining lymph nodes from CII-immunized mice contain high numbers of CII-specific B cells, which are isotype switched and V gene selected. In the present study we analyze the V region gene usage and epitope specificity of CII-reactive B cell hybridomas, randomly isolated from the primary and the secondary response in mice immunized with rat CII we make the following conclusions. 1) There are major epitopes in the native CII molecule to which the B cells preferentially respond. 2) B cells specific for the same epitope show a preferential pairing of certain VH/VK genes or a biased usage of individual VH (VHJ558 and VHX24) or VK genes (VK21). 3) The V genes are germ line encoded in the primary response and somatically mutated in the secondary response. Somatic mutations give the Abs cross-reactivity between CII epitopes, and epitope shift, i.e., another epitope within the CII molecule is recognized. 4) There is a sharing of certain V genes in B cell clones specific for different epitopes, indicating structural similarities of the different CII epitopes.
胶原诱导的关节炎是一种自身免疫性模型疾病，在用II型胶原（CII）免疫的DBA/1小鼠中诱发。T细胞和B细胞在关节炎的诱发中均起关键作用。CII免疫小鼠的引流淋巴结含有大量CII特异性B细胞，这些细胞发生了同种型转换并进行了V基因选择。在本研究中，我们分析了从用大鼠CII免疫的小鼠的初次和二次反应中随机分离的CII反应性B细胞杂交瘤的V区基因使用情况和表位特异性，得出以下结论。1）天然CII分子中存在B细胞优先应答的主要表位。2）对相同表位特异的B细胞显示出某些VH/VK基因的优先配对，或个别VH（VHJ558和VHX24）或VK基因（VK21）的偏向使用。3）V基因在初次反应中由种系编码，在二次反应中发生体细胞突变。体细胞突变使抗体具有CII表位之间的交叉反应性和表位转移，即识别CII分子内的另一个表位。4）对不同表位特异的B细胞克隆中存在某些V基因的共享，表明不同CII表位的结构相似性。
