Analysis of mutational lineage trees from sites of primary and secondary Ig gene diversification in rabbits and chickens
Analysis of mutational lineage trees from sites of primary and secondary Ig gene diversification in rabbits and chickens
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DOI：
10.4049/jimmunol.172.8.4790
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发表时间：
2004-04-15
影响因子：
4.4
通讯作者：
Mage, R
中科院分区：
文献类型：
--
作者：
Mehr, R;Edelman, H;Mage, R
B 淋巴细胞克隆中突变重排 Ig V 区序列的谱系树通常用于定性说明有关亲和力成熟动态的主张。在这项研究中，我们使用一种新方法来分析谱系树形状，使用图论术语来量化兔子和鸡的初级和次级多样化之间的差异。在这些物种中，Ig 基因多样化始于单个（鸡）或几个（兔子）V-H 基因的重排。体细胞超突变和基因转换有助于幼兔阑尾或胚胎和幼鸡法氏囊的初级多样化，以及生发中心（GC）免疫反应过程中的次级多样化。我们发现，至少在兔子中，阑尾中的初级多样化似乎以恒定的速率发生，并且脾 GC 中不存在 Ag 特异性选择的类型。这支持了这样的观点，即幼兔阑尾中不断扩大的克隆相关 B 细胞正在生成主要组库，并强调了肠道相关淋巴组织在哺乳动物免疫组库的早期发育中可能发挥的重要作用。此外，数据表明，与鼠类GC相比，兔和鸡GC中的超突变率更高，因此超突变和选择之间的平衡更倾向于突变，而不是选择。
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.