Biology subjects

Morelli, D. M.

Publications and source records attributed to Morelli, D. M..

2 recordsLinked to original sources

bioRxiv2025

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

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 {micro}m 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 non-cognate Ags. We found that while follicular B2 (Fo B), marginal zone, and B1 B cells are highly phagocytic of BCR-engaging targets through their BCR, only peritoneal cavity B1 cells could uptake non-cognate Ag-coated beads or bacteria. Despite this, B1 cells were not effective at presenting Ag to activate cognate T cells or at killing phagocytosed bacteria. Finally, analysis of scRNA-seq 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 non-cognate Ag uptake by Fo B cells. Our work will help contribute to a better understanding of non-classical Ag uptake mechanisms employed by B cells and their relevance to inflammation.

immunology↗

bioRxiv2022

Pre-Germinal Center Interactions with T Cells are Natural Checkpoints to Limit Autoimmune B Cell Responses

Interactions with antigen-specific T cells drive B cells activation and fate choices that ultimately determine the quality of high-affinity antibody responses. As such, thse interactions, and especially the long-lived interactions that occur prior to germinal center formation, may be important checkpoints to regulate undesirable responses. We directly observed interactions between T and B cells responding to the self-antigen Myelin Oligodendrocyte Glycoprotein (MOG) and found that they are of lower quality compared to interactions between cells responding to the model foreign antigen NP-ovalbumin (NP-OVA). This was associated with reduced expression of molecules that facilitate these interactions on the B cells but not on T cells. B cell expression of these molecules was not dictated by the T cell partner, nor could the relative lack of expression on MOG-sp. B cells be reversed by a multivalent antigen. Instead, MOG-sp. B cells were inherently less responsive to B cell Receptor stimulation than MOG-non-sp. cells. However, the phenotype of MOG-sp. B cells was not consistent with previous descriptions of autoimmune B cells that had been tolerized via regular exposure to systemically-expressed self-antigen. This suggests that alternate anergy pathways may exist to limit B cell responses to tissue-restricted self-antigens.

immunology↗