A transcriptomic signature of self-reactivity in the germinal center 2203

Abstract Description The critical role of the germinal centers (GC) in guiding lymphocyte response to foreign antigen via affinity maturation is well established. However, the mechanisms underpinning the dualistic function of GCs of avoiding self-reactivity are considerably less defined. B cells expressing self-reactive receptors have been recognized to enter the GC in response to foreign antigens mimicking self, with the B cells then acquiring mutations to decrease their self-reactivity, even at the expense of foreign binding. Although extensive work has explored the mechanisms potentiating increased foreign affinity within the GC, minimal studies have elucidated the processes which control loss of self-binding. By combining single cell RNA sequencing combined with antibody repertoire analysis in models tracing B cells with defined affinities to self and foreign antigens, we have characterized the cellular and transcriptomic phenotype of self-binding GC B cells as they progress on their affinity maturation pathway towards foreign and away from self-reactivity. We have defined a distinct molecular signature unique to this cellular subset. We have characterized how this distinct transcriptomic signature of self-reactivity in GC B cells changes as the cells are redeemed and lose their self-reactivity over time and defined biomarkers that could define redeemed cells that remain in circulation. Funding Sources NHMRC, NSW OHMR, Ramachiotti Foundation, UNSW SMBS, UNSW Cellulars Futures Institute Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)