Class switch recombination articles from across Nature Portfolio

B cell activation and differentiation entails metabolic remodelling, involving differential utilisation of monocarboxylates such as L-lactate and pyruvate. Here authors show by B-cell-specific genomic deletion of monocarboxylate transporter 1 (MCT1) that the consequential scarcity of pyruvate results in decreased acetylation of Histone H3 at K27, leading to decreased AID transcription and deficient class switching to IgG.

Class switch recombination (CSR) is a process by which B cells switch their immunoglobulin isotype and develop pathogen-eliminating antibodies. Here, the authors show that a protein kinase DYRK1A is required for protection from viral infection through the regulation of CSR and effective clonal expansion.

SHLD1, as a component of the Shieldin (SHLD) complex, mediates DNA repair via non-homologous end-joining (NHEJ), an essential process during lymphocyte development. Here the authors show that SHLD1 is actually dispensable for lymphocyte development and V(D)J recombination, but is essential for class-switching recombination in activated B cells.

Lanzavecchia and colleagues use single-cell B cell receptor sequencing to examine the clonal structure, stability and dynamics of the B cell repertoire and the relationship between memory B cells and newly generated plasma cells in humans.

IgD is expressed, predominantly together with IgM, via mRNA alternative splicing, but IgD class switch recombination (IgD CSR) has also been reported. Here the authors show, using Rad52-deficient mouse and human B cells, that IgD CSR is mediated by Rad52 through an alternative, microhomology-based end-joining pathway of DNA repair.

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.

Class-switch recombination was thought to take place in B cells that enter germinal centres, but this study shows that it actually occurs earlier than previously thought.

Shieldin is a newly characterized protein complex that functions downstream of 53BP1 in promoting NHEJ