Somatic hypermutation articles from across Nature Portfolio

Repeat vaccination with COVID-19 mRNA vaccines has been shown to increase breadth of the antibody response. Here the authors demonstrate that B cell clones induced by the ancestral COVID-19 vaccine develop into daughter clones with different reactivity to individual SARS-CoV-2 variants through the accumulation of somatic hypermutations.

Follicular helper T cells play critical roles in the formation of high affinity antibody responses, but the signals involved in the development of these cells after initial differentiation are poorly understood. Here Podestà, Cavazzoni and colleagues characterise transitionary phases of follicular helper T cell development and how progression through these stages is linked to humoral immunity.

Broadly neutralizing antibodies (bnAbs) for HIV have been difficult to elicit with one issue being the low B cell affinity required. Here the authors use a transgenic mouse bearing human-like antibody repertoires to show that low affinity B cells persist which enables vaccine expansion of antibodies against the CD4 binding site, a conserved HIV bnAb target.

Linterman and colleagues examine germinal center formation in older individuals. They find that aged T_FH cells have dysregulated CXCR4 expression, which causes spatial mislocalization of these cells in germinal centers, impairing their ability to provide help to B cells and to promote antibody production.

In this study, authors identified neutralizing antibodies by isolating B cells from SARS-CoV-2 Delta infected patients and detect altered structural features, likely introduced by somatic hypermutation, that are involved in epitope binding and increase neutralization breadth against virus variants.

SARS-CoV-2 vaccines and infection induce antibody responses but the evolution of subsequent variants has resulted in the development of escape mutants. Here the authors characterise, at single cell level, the antibody response in donors after a third dose of SARS-CoV-2 mRNA vaccination and show difference in breadth, neutralisation and molecular signature according to the vaccination regimen used.

A single-cell sequencing study shows that the human memory B cell repertoire is dominated by large IgM, IgG2 and IgA immunoglobulin families, whereas IgG1 families, including those specific for recall antigens, are of a small size. Multi-year analysis shows that memory B cell families are highly stable and that plasmablasts of T cell–independent and T cell–dependent isotypes are produced in a recurrent manner.

How B cell tolerance is retained during somatic hypermutation in germinal centers is incompletely understood. Two studies now show that Foxp3⁺ regulatory T cells undergo functional specialization to limit the magnitude of the germinal center response, and they may contribute to our understanding of how germinal center–mediated autoimmunity is prevented (pages 975–982 and 983–988).

Direct evaluation of the contribution of somatic hypermutation (SHM) to mucosal immunity has been hampered by the lack of models able to dissociate SHM from class-switch recombination, which are both dependent on the cytidine deaminase AID. A new mouse AID model now demonstrates the critical role of SHM in the control of gut bacteria.