Antibody responses against bacterial glycans affinity mature and diversify in germinal centers
Abstract
Anti-carbohydrate antibodies (Abs) play crucial roles in pathogen control, but their generation remains poorly understood. By studying responses toStreptococcus pyogenesin humans, we reveal that the glycan-targeted response shifts from IgM towards IgG and IgA memory with age and antigen exposure across blood, spleen, and tonsils. Both natural colonization and controlled human infection withS. pyogenesincreased class-switched B cells, with evidence of within-clone switching. Glycan-specific B cells readily participated in germinal center (GC) responses and showed robust somatic hypermutation despite a molecular signature consistent with receiving reduced T cell help. We conclude that mucosal pathogen encounters elicit glycan responses that class-switch, evolve and diversify through the GC. These findings reveal how age and infection history can influence the quality, quantity, and isotype use of glycan-specific B cells, with implications for the design and schedule of glycan-containing vaccines.
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