B-cell subsets have different capacities for phagocytosis and subsequent presentation of antigen to cognate T cells

Abstract B cells have been shown to be phagocytic under some circumstances. However, the phagocytic capacity of different B-cell subsets and how this is linked to antigen (Ag) presentation or other functions has not been characterized. To address this, we developed 2-µm phagocytic Ag-conjugated bead targets that target phagocytic pathways including the BCR, scavenger, Fc, and complement receptors to study potential pathways by which B cells phagocytose both cognate and noncognate Ags. We found that while follicular B2 (Fo B), marginal zone, and B1 cells are highly phagocytic of BCR-engaging targets through their BCR, only peritoneal cavity B1 cells could internalize noncognate Ag-coated beads or phagocytose and kill bacteria. Further, while all subsets were able to present cognate Ag to activate T cells, only B1 cells could present noncognate Ag. Finally, analysis of single-cell RNA sequencing data revealed that these differences in phagocytic capacity could not be explained by differential expression of relevant phagocytic receptors, implying that there is likely some form of regulation in place preventing noncognate Ag uptake by Fo B cells. Our work will help contribute to a better understanding of nonclassical Ag uptake mechanisms employed by B cells.