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

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. [Display omitted] •52 core V genes contribute to more than 99% of the antibody repertoire•V genes at both proximal and distal ends on the chromosome are preferably used•Shared clones between repertoires are underestimated because of undersampling•Motif RGYW-associated mutations tend to be positively selected The antibody repertoire plays a pivotal role in humoral immunity and has immense potential in fundamental research and clinical applications. The essential quantitative features of antibody repertoire are revealed and demonstrated by Yang et al. through the analyses of huge data and could serve as a reference for further studies.