Double-strand breaks in DNA generated during the normal assembly and diversification of lymphocyte antigen receptor genes or by genotoxic agents during infection activate DNA damage responses. Besides repairing damaged DNA, these responses trigger important signalling events that regulate immune cell development and function.

Diversification of the antibody repertoire is well known to be driven by genetic recombination and mutation. However, it is becoming apparent that other processes can also diversify antibody specificities. Here, Dimitrov and colleagues discuss these unconventional strategies for antibody diversification and consider why these extra strategies have evolved.

A genetic study of the baseline human antibody repertoire, based on the circulating B cell populations of ten subjects, reveals universally shared antibody clonotypes within repertoires that are largely unique to the individual.

VDJ-seq is a DNA-based, high-throughput sequencing method that uses biotinylated J gene primers and UMIs to quantify immunoglobulin diversity in an unbiased manner on a per-cell basis.

T cell receptors are generated by somatic gene recombination, and are normally selected against autoreactivity. Here the authors show that CD4 T cells from patients with autoimmune type 1 diabetes have shorter TCRβ sequences, broader repertoire diversity, and more repertoire sharing than those from healthy individuals.