Meffre Eric, Wardemann Hedda
Hospital for Special Surgery, Weill Medical College of Cornell University, New York, NY 10021, USA.
Curr Opin Immunol. 2008 Dec;20(6):632-8. doi: 10.1016/j.coi.2008.09.001. Epub 2008 Oct 25.
The enormous diversity of the antibody repertoire is generated by two mechanisms: recombination of immunoglobulin (Ig) gene variable (V), diversity (D), and joining (J) gene segments during the early stages of B-cell development in the bone marrow and somatic hypermutation (SHM) of functional Ig genes from antigen-activated B cells within secondary lymphoid organs. Diversity by V(D)J recombination and SHM not only provides protective humoral immunity but also generates potentially harmful clones expressing autoantibodies. Under normal circumstances, several mechanisms regulate the removal of autoreactive B cells and defects in central and peripheral B cell tolerance checkpoints are associated with the development of autoimmunity in humans.
在骨髓中B细胞发育的早期阶段，免疫球蛋白（Ig）基因可变（V）、多样（D）和连接（J）基因片段的重组，以及二级淋巴器官内抗原激活的B细胞功能性Ig基因的体细胞超突变（SHM）。通过V（D）J重组和SHM产生的多样性不仅提供保护性体液免疫，还产生表达自身抗体的潜在有害克隆。在正常情况下，多种机制调节自身反应性B细胞的清除，而中枢和外周B细胞耐受检查点的缺陷与人类自身免疫性疾病的发生有关。
