The Usage of Human IGHJ Genes Follows a Particular Non-random Selection: The Recombination Signal Sequence May Affect the Usage of Human IGHJ Genes

Frontiers in Genetics

Qingqing Ma¹  Long Ma¹  Juan Pan¹  Danhua Su¹  Jiang Yu²  Xiaoheng Dong³  Xinsheng Yao³  Suhong Sun³  Xiaomei Wang³  Xiaoyan He³  Bin Shi⁵ 

[1] Practice Base for Graduate Students Education, Zunyi Medical University, Zunyi, China;Department of Breast Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China;;Department of Immunology, Center of Immunomolecular Engineering, Innovation &Department of Laboratory Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, China;School of Laboratory Medicine, Zunyi Medical University, Zunyi, China;

关键词: High-throughput sequencing;    V(D)J;    IGHJ;    “12/23” rule;    BCR;   

DOI  :  10.3389/fgene.2020.524413

来源: DOAJ

【 摘 要 】

The formation of the B cell receptor (BCR) heavy chain variable region is derived from the germline V(D)J gene rearrangement according to the “12/23” rule and the “beyond 12/23” rule. The usage frequency of each V(D)J gene in the peripheral BCR repertoires is related to the initial recombination, self-tolerance selection, and the clonal proliferative response. However, their specific differences and possible mechanisms are still unknown. We analyzed in-frame and out-of-frame BCR-H repertoires from human samples with normal physiological and various pathological conditions by high-throughput sequencing. Our results showed that IGHJ gene frequency follows a similar pattern which is previously known, where IGHJ4 is used at high frequency (>40%), IGHJ6/IGHJ3/IGHJ5 is used at medium frequencies (10∼20%), and IGH2/IGHJ1 is used at low frequency (<4%) under whether normal physiological or various pathological conditions. However, our analysis of the recombination signal sequences suggested that the conserved non-amer and heptamer and certain 23 bp spacer length may affect the initial IGHD-IGHJ recombination, which results in different frequencies of IGHJ genes among the initial BCR-H repertoire. Based on this “initial repertoire,” we recommend that re-evaluation and further investigation are needed when analyzing the significance and mechanism of IGHJ gene frequency in self-tolerance selection and the clonal proliferative response.

【 授权许可】

Unknown