Foreman Angela Lee, Van de Water Judy, Gougeon Marie-Lise, Gershwin M Eric
Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA 95616, USA.
Autoimmun Rev. 2007 Jun;6(6):387-401. doi: 10.1016/j.autrev.2006.12.005. Epub 2007 Jan 12.
The role of B cells in autoimmune diseases has not been fully elucidated. It is also unclear whether breaking of B cell tolerance in patients with autoimmune diseases is due to underlying defects in the molecular mechanisms involved in the arrangement of antibody genes or deficiencies in the subsequent selective influences that shape the antibody repertoire. Analysis of immunoglobulin (Ig) variable (V) gene usage is beginning to provide answers to some of these questions. Such analyses have identified some differences in the basic Ig V gene repertoire of patients with autoimmune diseases compared to healthy controls, even though none of these differences can be considered major. Defects in positive and negative selection, mutational targeting and, in some cases, receptor editing have also been detected. In addition, analysis of Ig V gene usage in target organs and tissues of patients with autoimmune diseases has clearly demonstrated that there is a highly compartmentalized clonal expansion of B cells driven by a limited number of antigens in these tissues. Great progress has been made in the structural and functional characterization of disease-associated antibodies, largely because of the development of the combinatorial library technique. Use of antibodies generated by this technique offers great promise in identifying B cell epitopes on known target antigens and in gaining greater insights into the pathogenic role of B cells in both B and T cell mediated autoimmune diseases.
B细胞在自身免疫性疾病中的作用尚未完全阐明。自身免疫性疾病患者B细胞耐受性的打破是由于抗体基因排列所涉及的分子机制存在潜在缺陷，还是由于塑造抗体库的后续选择性影响存在缺陷，目前也尚不清楚。对免疫球蛋白（Ig）可变（V）基因使用情况的分析开始为其中一些问题提供答案。此类分析已确定，与健康对照相比，自身免疫性疾病患者的基本Ig V基因库存在一些差异，尽管这些差异都不能被视为主要差异。还检测到了阳性和阴性选择、突变靶向以及某些情况下受体编辑方面的缺陷。此外，对自身免疫性疾病患者靶器官和组织中Ig V基因使用情况的分析清楚地表明，这些组织中存在由有限数量抗原驱动的B细胞高度分隔的克隆性扩增。在疾病相关抗体的结构和功能表征方面已取得了很大进展，这在很大程度上归功于组合文库技术的发展。使用该技术产生的抗体在识别已知靶抗原上的B细胞表位以及更深入了解B细胞在B细胞和T细胞介导的自身免疫性疾病中的致病作用方面具有很大潜力。
