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对II型胶原蛋白上特定表位具有特异性的表达免疫球蛋白G的B细胞可变区基因选择

Variable region gene selection of immunoglobulin G-expressing B cells with specificity for a defined epitope on type II collagen.

作者信息

Mo J A, Bona C A, Holmdahl R

机构信息

Department of Medical and Physiological Chemistry, Uppsala University, Sweden.

出版信息

Eur J Immunol. 1993 Oct;23(10):2503-10. doi: 10.1002/eji.1830231019.

DOI:10.1002/eji.1830231019
PMID:7691608
Abstract

Immunization with type II collagen (CII) induces collagen-induced arthritis (CIA) in animals, and B cells reactive with CII are involved in the induction and manifestation of the disease. In this study, B cell hybridomas producing IgG antibodies specific for a major epitope on mouse CII (the "C1" epitope, amino acid 316-333), were isolated 11 days after immunization from draining lymph nodes in DBA/1 mice. Injection into neonatal mice of purified and biotinylated monoclonal antibodies binding the C1 epitope led to a specific binding to joint cartilage, demonstrating that the antibodies interact with native antigen in vivo. cDNA sequencing of the B cell clones revealed that they all expressed the same combination of a variable heavy chain (VH J558 family) and light chain (V kappa 21 family) germ-line gene, apparently lacking somatic mutations. The presence of isotype-switched B cells expressing a certain combination of V genes encoding antibodies that bind epitopes in vivo, indicates that this B cell population has been peripherally selected.

摘要

用II型胶原蛋白(CII)免疫可在动物中诱发胶原诱导的关节炎(CIA),与CII反应的B细胞参与该疾病的诱导和表现。在本研究中,于免疫后11天从DBA/1小鼠的引流淋巴结中分离出产生针对小鼠CII上主要表位(“C1”表位,氨基酸316 - 333)的IgG抗体的B细胞杂交瘤。将结合C1表位的纯化生物素化单克隆抗体注射到新生小鼠体内,导致其与关节软骨特异性结合,表明这些抗体在体内与天然抗原相互作用。对B细胞克隆进行cDNA测序显示,它们均表达可变重链(VH J558家族)和轻链(Vκ21家族)种系基因的相同组合,明显缺乏体细胞突变。表达编码在体内结合表位的抗体的特定V基因组合的同种型转换B细胞的存在,表明该B细胞群体已在外周被选择。

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