State Key Laboratory of Biotherapy, West China Hospital, Collaborative Innovation Center and Sichuan University, Chengdu, China.
Laboratory of Aquatic Molecular Biology and Biotechnology, Department of Aquatic Bioscience, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
Front Immunol. 2018 Feb 21;9:251. doi: 10.3389/fimmu.2018.00251. eCollection 2018.
B-cell antigen receptor (BCR) or antibody diversity arises from somatic recombination of immunoglobulin (Ig) gene segments and is concentrated within the Ig heavy (H) chain complementarity-determining region 3 (CDR-H3). We performed high-throughput sequencing of the expressed antibody heavy-chain repertoire from adult torafugu. We found that torafugu use between 70 and 82% of all possible V (variable), D (diversity), and J (joining) gene segment combinations and that they share a similar frequency distribution of these VDJ combinations. The CDR-H3 sequence repertoire observed in individuals is biased with the preferential use of a small number of VDJ, dominated by sequences containing inserted nucleotides. We uncovered the common CDR-H3 amino-acid (aa) sequences shared by individuals. Common CDR-H3 sequences feature highly convergent nucleic-acid recombination compared with private ones. Finally, we observed differences in repertoires between IgM and IgT, including the unequal usage frequencies of V gene segment and the biased number of nucleotide insertion/deletion at VDJ junction regions that leads to distinct distributions of CDR-H3 lengths.
B 细胞抗原受体 (BCR) 或抗体多样性源于免疫球蛋白 (Ig) 基因片段的体细胞重组，集中在 Ig 重链互补决定区 3 (CDR-H3) 内。我们对成年河豚的表达抗体重链库进行了高通量测序。我们发现，河豚使用了所有可能的 V（可变）、D（多样性）和 J（连接）基因片段组合的 70%至 82%，并且它们具有相似的 VDJ 组合频率分布。个体中观察到的 CDR-H3 序列库存在偏倚，优先使用少数 VDJ，主要由包含插入核苷酸的序列组成。我们揭示了个体共有的常见 CDR-H3 氨基酸 (aa) 序列。与私有序列相比，常见的 CDR-H3 序列具有高度趋同的核酸重组。最后，我们观察到 IgM 和 IgT 之间的库差异，包括 V 基因片段的使用频率不均，以及 VDJ 连接处核苷酸插入/缺失的偏向性，导致 CDR-H3 长度的分布不同。
