Mehr Ramit, Edelman Hanna, Sehgal Devinder, Mage Rose
Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
J Immunol. 2004 Apr 15;172(8):4790-6. doi: 10.4049/jimmunol.172.8.4790.
Lineage trees of mutated rearranged Ig V region sequences in B lymphocyte clones often serve to qualitatively illustrate claims concerning the dynamics of affinity maturation. In this study, we use a novel method for analyzing lineage tree shapes, using terms from graph theory to quantify the differences between primary and secondary diversification in rabbits and chickens. In these species, Ig gene diversification starts with rearrangement of a single (in chicken) or a few (in rabbit) V(H) genes. Somatic hypermutation and gene conversion contribute to primary diversification in appendix of young rabbits or in bursa of Fabricius of embryonic and young chickens and to secondary diversification during immune responses in germinal centers (GCs). We find that, at least in rabbits, primary diversification appears to occur at a constant rate in the appendix, and the type of Ag-specific selection seen in splenic GCs is absent. This supports the view that a primary repertoire is being generated within the expanding clonally related B cells in appendix of young rabbits and emphasizes the important role that gut-associated lymphoid tissues may play in early development of mammalian immune repertoires. Additionally, the data indicate a higher rate of hypermutation in rabbit and chicken GCs, such that the balance between hypermutation and selection tends more toward mutation and less toward selection in rabbit and chicken compared with murine GCs.
B淋巴细胞克隆中突变重排的Ig V区序列的谱系树常被用于定性说明有关亲和力成熟动力学的观点。在本研究中，我们使用一种分析谱系树形状的新方法，运用图论术语来量化兔和鸡的初次多样化与二次多样化之间的差异。在这些物种中，Ig基因多样化始于单个（鸡）或少数（兔）V(H)基因的重排。体细胞超突变和基因转换在幼兔的阑尾或胚胎期及幼鸡的法氏囊中促成初次多样化，并在生发中心（GCs）的免疫反应期间促成二次多样化。我们发现，至少在兔中，初次多样化在阑尾中似乎以恒定速率发生，且在脾生发中心所见的抗原特异性选择类型并不存在。这支持了这样一种观点，即在幼兔阑尾中不断扩增的克隆相关B细胞内正在产生一个初始库，并强调了肠道相关淋巴组织在哺乳动物免疫库早期发育中可能发挥的重要作用。此外，数据表明兔和鸡的生发中心超突变率更高，因此与鼠生发中心相比，兔和鸡的超突变与选择之间的平衡更倾向于突变而非选择。
