Langille, M. | bioRxiv Science

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↗

bioRxiv2023

Profiling novel lateral gene transfer events in the human microbiome

Lateral gene transfer (LGT) is an important mechanism for genome diversification in microbial populations, including the human microbiome. While prior work has surveyed LGT events in human-associated microbial isolate genomes, the scope and dynamics of novel LGT events arising in personal microbiomes are not well understood, as there are no widely adopted computational methods to detect, quantify, and characterize LGT from complex microbial communities. We addressed this by developing, benchmarking, and experimentally validating a computational method (WAAFLE) to profile novel LGT events from assembled metagenomes. Applying WAAFLE to >2K human metagenomes from diverse body sites, we identified >100K putative high-confidence but previously uncharacterized LGT events ([~]2 per assembled microbial genome-equivalent). These events were enriched for mobile elements (as expected), as well as restriction-modification and transport functions typically associated with the destruction of foreign DNA. LGT frequency was quantifiably influenced by biogeography, the phylogenetic similarity of the involved taxa, and the ecological abundance of the donor taxon. These forces manifest as LGT networks in which hub species abundant in a community type donate unequally with their close phylogenetic neighbors. Our findings suggest that LGT may be a more ubiquitous process in the human microbiome than previously described. The open-source WAAFLE implementation, documentation, and data from this work are available at http://huttenhower.sph.harvard.edu/waafle.

bioinformatics↗