蝙蝠IG H/L/K基因座的注释和蝙蝠BCR-CDR3谱的特征分析
Annotation of bat IG H/L/K loci and analysis of the characteristics of bat BCR-CDR3 repertoires.
摘要(中文译文)
蝙蝠是哺乳动物中第二大目，也是唯一会飞的哺乳动物，具有病毒耐受、长寿和低肿瘤发生率等显著生物学特征。尽管蝙蝠是众多人畜共患病毒的储存宿主，但它们保持无症状且无明显的感染表现。然而，蝙蝠B细胞适应性免疫应答的机制和效应在很大程度上仍不清楚。在哺乳动物中，BCR V(D)J基因重排和CDR3库的形成是B细胞多样性、特异性和记忆应答的关键机制。本研究首次对蝙蝠的IGK基因座（17个KV；4个KJ；1个LC）和IGL基因座（74个LV；6个LJ-LC基因簇）进行了染色体水平注释，同时对另一种蝙蝠的IGH基因座（81个HV；16个HD；6个HJ；IgM、IgG、IgE、IgA的HC）和IGL基因座（56个LV；9个LJ-LC基因簇）进行了注释，并对各IG基因座进行了比较进化分析。利用注释的IG H/K/L恒定区基因序列，我们采用5'cDNA末端快速扩增技术（5'RACE）构建BCR CDR3库并进行高通量测序（HTS）。随后利用注释的蝙蝠IG H/K/L基因构建了用于蝙蝠BCR CDR3高通量测序分析的MixCR工具。在两种蝙蝠的脾脏和肠道组织中，我们观察到BCR CDR3库中V基因和J基因具有高度多样性和差异性的优先使用。与人和小鼠的BCR CDR3库相比，蝙蝠CDR3库既表现出相似性（如高频基序、酪氨酸富集），也表现出明显差异（如N/P核苷酸添加/缺失模式、CDR3区氨基酸分布）。本研究提供了不同科蝙蝠IG基因座的染色体水平注释，并初步揭示了蝙蝠BCR-CDR3库的基本特征及其与人和小鼠的关键差异。我们的发现为未来深入研究蝙蝠B细胞适应性免疫应答提供了比较基础数据、新见解、工具和策略。
Abstract
Bats represent the second largest order of mammals and are the only flying mammals, exhibiting remarkable biological characteristics such as viral tolerance, longevity, and low tumor incidence. Although bats serve as reservoirs for numerous zoonotic viruses, they remain asymptomatic without overt infection. However, the mechanisms and effects of B-cell adaptive immune responses in bats are largely unknown. In mammals, BCR V(D)J gene recombination and the formation of the CDR3 repertoire are key mechanisms underlying B-cell diversity, specificity, and memory responses. In this study, we performed, for the first time, a chromosome-level annotation of the IGK locus (17 KV; 4 KJ;1 LC) and IGL locus (74 LV; 6 LJ-LC gene clusters) in , as well as the IGH locus (81 HV; 16 HD; 6 HJ;HC of IgM, IgG, IgE, IgA) and IGL locus (56 LV; 9 LJ-LC gene clusters) in Comparative evolutionary analyses of each IG locus were also conducted. Using the annotated IG H/K/L constant region gene sequences, we employed 5' Rapid Amplification of cDNA Ends (5'RACE) to construct BCR CDR3 repertoires and perform high-throughput sequencing (HTS). The annotated bat IG H/K/L genes were then used to build a MixCR tool for bat BCR CDR3 HTS analysis. In the spleen and intestinal tissues of bats from and , we observed high diversity and differential preferential usage of V and J genes in the BCR CDR3 repertoires. Compared with human and mouse BCR CDR3 repertoires, bat CDR3 repertoires exhibited both similarities (e.g., high-frequency motifs, tyrosine enrichment) and distinct differences (e.g., N/P nucleotide Additions/Deletions patterns, amino acid distribution in the CDR3 region). This study provides chromosome-level annotations of IG loci in bats from different families and preliminarily reveals the fundamental characteristics of the bat BCR-CDR3 repertoire, along with key differences compared to human and mouse. Our findings offer comparative base-data, novel insights, tools, and strategies for future in-depth investigations into B-cell adaptive immune responses in bats.
如何引用
AMA
QinLu Liu, Long Ma, Jun Li, LongYu Liu, Hao Zhou, ZeGang Liu, et al. Annotation of bat IG H/L/K loci and analysis of the characteristics of bat BCR-CDR3 repertoires.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1827051.
APA
QinLu Liu, Long Ma, Jun Li, LongYu Liu, Hao Zhou, ZeGang Liu, et al (2026). Annotation of bat IG H/L/K loci and analysis of the characteristics of bat BCR-CDR3 repertoires.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1827051
GB/T 7714
QinLu Liu, Long Ma, Jun Li, LongYu Liu, Hao Zhou, ZeGang Liu, et al. Annotation of bat IG H/L/K loci and analysis of the characteristics of bat BCR-CDR3 repertoires.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1827051.
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