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.

Knowledge on how antibody responses have evolved is critical for the induction of protective immunity. Here the authors analyse, using high-throughput sequencing of both exon and intron regions, the mutation and lineage development of an HIV-neutralizing antibody to find an unexpected early emergence of broadly neutralizing species.

Activation-induced deaminase (AID) is important for inducing desirable mutations at the B cell receptor genes for effective antibody responses. Here the authors show that three key arginine residues of AID link AID-chromatin association with transcription elongation to license AID for specific mutagenesis in B cells.

Somatic hypermutation of antibodies can occur in infants but are difficult to track. Here the authors present a new method called MIDCIRS for deep quantitative repertoire sequencing with few cells, and show infants as young as 3 months can expand antibody lineage complexity in response to malaria infection.

B-cell VH region repertoire sequencing of eight anatomical sites in six human donors reveals distinct networks of clone distribution.