B cell dynamics of long-lived germinal centers 3367

Abstract Description Long-lived germinal centers (LLGCs) form in secondary lymphoid organs in response to certain viral infections and could represent a potential source of highly mutated B cells. Studies characterizing the dynamics and properties of virus-primed B cells and their progenies are scarce, representing a major gap in our knowledge of LLGCs. In this study, we show that, rather than consisting of continuously evolving B cell clones, LLGCs elicited by influenza virus or SARS-CoV-2 infection in mice are sustained by progressive replacement of founder clones by naïve-derived invader B cells that do not detectably bind viral antigens. Rare founder clones that resist replacement for long periods are enriched in clones with heavily mutated immunoglobulins, including some with very high affinity for antigen, that can be recalled by boosting. Our findings reveal underappreciated aspects of the biology of LLGCs generated by respiratory virus infection and identify clonal replacement as a potential constraint on the development of highly mutated antibodies within these structures (de Carvalho et al, Cell, 2023). Funding Sources HFSP fellowship LT000892/2020-L NIH grant DP1AI1442 NIH/NIAID grants R01AI119006, R01AI139117, and R01AI157137 Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)