Abstract Text: Amongst the diverse functions of B cells, a small literature suggests that these cells have the capacity to drive CD8+ T cell responses via cross-presentation of exogenous antigens. In this study, we investigate whether alloantigen-stimulated human B cells demonstrate characteristics required for antigen cross-presentation. Using a combination of transcriptional, immunofluorescence and multi-color flow cytometric analyses of responder B cells in mixed lymphocyte reactions (MLRs), we identified and characterized the emergence of a subpopulation of activated (CD86+) B cells characterized by FcRL5 expression. FcRL5+CD86+ B cells show significantly higher expression of molecules associated with processing and presenting endocytosed antigens consistent with putative antigen cross-presenting functionality (pCP B cells). The proportion of such pCP B cells correlated with the proportion of granzyme B+ perforin+ cytotoxic CD8+ T cells in MLRs. Consistent with a requirement for uptake and processing of exogenous allo-antigenic material, pCP B cells demonstrate significantly higher phagocytic capacity in endocytosis assays. We also identified a subpopulation of B cells with these pCP B cell characteristics in disaggregated but otherwise unmanipulated human splenocytes, showing that such cells can be found in vivo. In conclusion, we have identified a distinctive subpopulation of human B cells with features consistent with a role in allo-antigen cross-presentation. Further investigation of this B cell subset could lay the foundation for identification of biomarkers and targeted therapeutics relevant to curbing the contributions of pCP-B cells to alloresponsiveness and minimizing morbidity in post-transplant patients.
