Dynamics of heavy chain junctional length biases in antibody repertoires

Antibody variable domain sequence diversity is generated by recombination of germline segments. The third complementarity-determining region of the heavy chain (CDR H3) is the region of highest sequence diversity and is formed by the joining of heavy chain V H , D H and J H germline segments combined with random nucleotide trimming and additions between these segments. We show that CDR H3 and junctional segment length distributions are biased in human antibody repertoires as a function of V H , V L and J H germline segment utilization. Most length biases are apparent in the naive and antigen experienced B cell compartments but not in nonproductive recombination products, indicating B cell selection as a major driver of these biases. Our findings reveal biases in the antibody CDR H3 diversity landscape shaped by V H , V L , and J H germline segment use during naive and antigen-experienced repertoire selection. Sankar et al. investigate the junctional length biases (determining antibody binding potential) as a function of germline gene usage in antibody repertoires. They show that CDR H3 and junction length are biased by V H , V L , and J H germline segment usage and these biases are apparent in both naive and antigen-experienced repertoires but not in non-productive repertoires.