Deciphering the impact of human early B cell responses on long-lived antibody responses

Early human B cell response, including the extrafollicular (EF) response, are poorly characterised but have a vital role in rapid antibody production. I propose that this pathway has longer-term consequences in the lymph node (LN) microenvironment and metabolite availability affecting cell fate. This project will integrate human in vivo fine-needle aspirant samples with ex vivo LN culture slice models to characterise and validate differentiating human early B cell trajectories. Spatial transcriptomics, complemented by multiplex imaging, will spatially verify a transcriptomic EF B cell gene signature. Early B cells in human LNs responding to a primary antigen encounter from a xenogenic protein challenge study will be characterised by scRNAseq and clonal analysis. The recall memory response and prediction potential of early human B cells will be evaluated by an intradermal re-challenge using in situ hybridization. Computational metabolism analysis with ex vivo LN slice functional validation will determine metabolic differences distinguishing early B cell fates and how they can be altered. Together, I will address a fundamental immunological question about early human B cells and their impact on long-lived antibodies. Findings may facilitate tailored next-generation vaccination and adjuvant strategies to enhance long-term memory responses.