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Human Anti-Glycan Reactivity is Driven by the Selection of B cells Utilizing Private Antibody Gene Rearrangements

J Stewart New1, Christopher F Fucile2, Amanda R Callahan1

  • 1Department of Microbiology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham AL 35294, USA.

Biorxiv : the Preprint Server for Biology
|October 28, 2024
PubMed

The human antibody repertoire is broadly reactive with carbohydrate antigens represented in the universe of all living things, including both the host/self- as well as the commensal microflora-derived glycomes. Here we have used BCR receptor cloning and expression together with single-cell transcriptomics to analyze the B cell repertoire to the ubiquitous N-acetyl-D-glucosamine (GlcNAc) epitope in human cohorts and dissect the immune phylogeny of this predominant class of antibodies. We find that circulating anti-GlcNAc B cells exhibiting canonical BMem phenotypes emerge rapidly after birth and couple this observation with evidence for germinal center-dependent affinity maturation of carbohydrate-specific B cell receptors in situ during early childhood. Direct analysis of individual B cell clonotypes reveals they exhibit strikingly distinct fine-specificity profiles for palettes of GlcNAc containing moieties. These results suggest that a generalized exposure to complex environmental glycans drives the steady state anti-glycan repertoire.

Keywords:
Anti-carbohydrate antibodyB cell repertoireGerminal CenterMemory B cellsN-acetyl-D-glucosamineNeonatal Immunity

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