Defining critical roles for RNA-binding proteins (RBPs) in B cells undergoing antibody gene diversification
B cells are crucial to immune defence by producing large quantities of antibodies with pathogen neutralizing capacities, when terminally differentiated into plasma cells. Effective antibody responses are tailored and can be made to target a limitless range of antigens with exquisite specificity. This remarkable ability of the adaptive immune system relies on the generation of a diverse repertoire of antibodies, which goes hand-in-hand with B cell development.
Antibodies are encoded by immunoglobulin heavy (IgH) and light (IgL) chain loci, which go through processes of DNA deletion-recombination – V(D)J recombination, class switch recombination (CSR) - and somatic hypermutation (SHM), at different stages of B cell development. Our research focuses on the role of RBPs at B cell developmental-stages when V(D)J recombination and CSR occur. Control over mRNA metabolism or regulation of RNA function by RBPs is particularly relevant at these steps, as important cellular decisions – programmed induction of DNA mutation/breaks at immunoglobulin genes, cell proliferation, cell differentiation – rely on tight regulation of gene expression and the maintenance of genome stability.
Understanding the molecular mechanisms regulating antibody production is important, as impaired ability to generate a diverse antibody repertoire often results in immunodeficient or autoimmune conditions. Our work also has potential implications for other pathological outcomes associated with antibody gene diversification, as for example the development of B cell lymphomas. In the future, RBPs may constitute ideal targets to modulate B cell function during vaccination or disease, and this will require a better understanding of their roles in B cell biology.