Anti-Glycan Reactivity in Humans is Driven by the Selection of B cells Utilizing Private Antibody Gene Rearrangements that are Affinity Maturated in Germinal Centers
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ABSTRACT: 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 evolutionary history 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.
ORGANISM(S): Homo sapiens
PROVIDER: GSE278639 | GEO | 2025/10/01
REPOSITORIES: GEO
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