Human Anti-Glycan Reactivity is Driven by the Selection of B cells Utilizing Private Antibody Gene Rearrangements that are Affinity Maturated in Germinal Centers

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.