Large-scale analysis of 2,152 Ig-seq datasets reveals key features of B cell biology and the antibody repertoire

Abstract

Antibody repertoire sequencing enables researchers to acquire millions of B cell receptors and investigate these molecules at the single-nucleotide level. This power and resolution in studying humoral responses have led to its wide applications. However, most of these studies were conducted with a limited number of samples. Given the extraordinary diversity, assessment of these key features with a large sample set is demanded. Thus, we collect and systematically analyze 2,152 high-quality heavy-chain antibody repertoires. Our study reveals that 52 core variable genes universally contribute to more than 99% of each individual's repertoire; a distal interspersed preferences characterize V gene recombination; the number of public clones between two repertoires follows a linear model, and the positive selection dominates at RGYW motif in somatic hypermutations. Thus, this population-level analysis resolves some critical features of the antibody repertoire and may have significant value to the large cadre of scientists.

Keywords: B cell biology; Ig-seq; antibody repertoire; high-throughput sequencing; large-scale analysis.