School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.
Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, United States.
Front Immunol. 2018 Oct 8;9:2249. doi: 10.3389/fimmu.2018.02249. eCollection 2018.
Discussion of the antibody repertoire usually emphasizes diversity, but a conspicuous feature of the light chain repertoire is its lack of diversity. The diversity of reported allelic variants of germline light chain genes is also limited, even in well-studied species. In this review, the implications of this lack of diversity are considered. We explore germline and rearranged light chain genes in a variety of species, with a particular focus on human and mouse genes. The importance of the number, organization and orientation of the genes for the control of repertoire development is discussed, and we consider how primary rearrangements and receptor editing together shape the expressed light chain repertoire. The resulting repertoire is dominated by just a handful of IGKV and IGLV genes. It has been hypothesized that an important function of the light chain is to guard against self-reactivity, and the role of secondary rearrangements in this process could explain the genomic organization of the light chain genes. It could also explain why the light chain repertoire is so limited. Heavy and light chain genes may have co-evolved to ensure that suitable light chain partners are usually available for each heavy chain that forms early in B cell development. We suggest that the co-evolved loci of the house mouse often became separated during the inbreeding of laboratory mice, resulting in new pairings of loci that are derived from different sub-species of the house mouse. A resulting vulnerability to self-reactivity could explain at least some mouse models of autoimmune disease.
讨论抗体库时通常强调多样性，但轻链库的一个显著特征是其缺乏多样性。报道的 germline 轻链基因的等位变体多样性也很有限，即使在研究充分的物种中也是如此。在这篇综述中，我们考虑了这种缺乏多样性的影响。我们研究了多种物种的 germline 和重排轻链基因，特别关注人类和小鼠基因。我们讨论了基因的数量、组织和定向对库发育控制的重要性，并考虑了初级重排和受体编辑如何共同塑造表达的轻链库。由此产生的库主要由少数几个 IGKV 和 IGLV 基因组成。有人假设轻链的一个重要功能是防止自身反应，而次级重排在这个过程中的作用可以解释轻链基因的基因组组织。这也可以解释为什么轻链库如此有限。重链和轻链基因可能共同进化，以确保在 B 细胞发育早期形成的每个重链通常都有合适的轻链伴侣。我们认为，家鼠的共同进化基因座在实验室小鼠的近交过程中经常分离，导致来自不同家鼠亚种的新基因座配对。由此产生的自身反应易感性至少可以解释一些自身免疫疾病的小鼠模型。
