The usage of human IGHJ genes follows a particular nonrandom selection: The recombination signal sequence affects the usage of human IGHJ genes

Abstract

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 physiological and various pathological conditions by high-throughputsequencing. Our results showed that IGHJ gene frequency follows a similar pattern 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 physiological or various pathological conditions. Furthermore, analysis of the recombination signal sequences suggested that the conserved nonamer 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 "background 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.

Landscapes and dynamic diversifications of B-cell receptor repertoires in COVID-19 patients

“…The IGHV3-74, IGHV4-34 and IGHV4-39 in COVID-19 patients showed more abundant than that of healthy controls. Preferred J gene segments showed a high degree of consistency among all time points in both patients and healthy donors (Fig 1 g), with the most frequent J segment is IGHJ4, this is consistent with previously report [21] . For each individual, the frequency of distinct gene segments usage over the infection time course was fairly stable, shown as high correlations in the heatmap of Fig preprint (which was not certified by peer review) is the author/funder.…”

Genomic features of humoral immunity support tolerance model in Egyptian rousette bats

“…The expansion of the IGHJ4 genes in ERBs may reflect its important role in V(D)J recombination; however, its impact in B cell diversity and antibody specificity is still unknown (Arnaout et al, 2011). Despite humans containing only a single IGHJ4, it is the most commonly used J segment (Shi et al, 2020).…”