Protection and neutralization of a vast array of pathogens is accomplished by the tremendous diversity of the B cell receptor (BCR) repertoire. For jawed vertebrates, this diversity is initiated via the somatic recombination of immunoglobulin (Ig) germline elements. While it is clear that the number of these germline segments differs from species to species, the extent of cross-species sequence diversity remains largely uncharacterized. Here we use extensive computational and statistical methods to investigate the sequence diversity and evolutionary relationship between Ig variable (V), diversity (D), and joining (J) germline segments across nine commonly studied species ranging from zebrafish to human. Metrics such as guanine-cytosine (GC) content showed low redundancy across Ig germline genes within a given species. Other comparisons, including amino acid motifs, evolutionary selection, and sequence diversity, revealed species-specific properties. Additionally, we showed that the germline-encoded diversity differs across antibody (recombined V-D-J) repertoires of various B cell subsets. To facilitate future comparative immunogenomics analysis, we created VDJgermlines, an R package that contains the germline sequences from multiple species. Our study informs strategies for the humanization and engineering of therapeutic antibodies.

中文翻译：

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种间和种内系统发育指纹和免疫球蛋白可变基因序列多样性的比较。

B细胞受体（BCR）库的多样性极大地实现了对多种病原体的保护和中和。对于颌骨脊椎动物，这种多样性是通过免疫球蛋白（Ig）种系元素的体细胞重组而引发的。显然，这些种系片段的数量因物种而异，但跨物种序列多样性的程度仍未得到充分表征。在这里，我们使用广泛的计算和统计方法来研究从斑马鱼到人类的9种常见物种的Ig变量（V），多样性（D）和连接（J）种系片段之间的序列多样性和进化关系。诸如鸟嘌呤-胞嘧啶（GC）含量之类的指标在给定物种内的Ig生殖系基因之间显示出较低的冗余度。其他比较 包括氨基酸基序，进化选择和序列多样性，揭示了物种特异性的特性。此外，我们显示了不同B细胞亚群的抗体（重组VDJ）库中种系编码的多样性不同。为了促进将来的比较免疫基因组学分析，我们创建了VDJgermlines，这是一个R包，其中包含来自多个物种的种系序列。我们的研究为治疗性抗体的人源化和工程化提供了策略。一个R包，其中包含多个物种的种系序列。我们的研究为治疗性抗体的人源化和工程化提供了策略。一个R包，其中包含多个物种的种系序列。我们的研究为治疗性抗体的人源化和工程化提供了策略。