Anti-carbohydrate antibodies (Abs) are crucial in pathogen control and believed to form through a distinct pathway from protein-targeting responses, emerging early without T cell interactions. Group A Carbohydrate (GAC) from S. pyogenes is a key candidate antigen for multi-component vaccines. However, the development and maturation of glycan and protein antigen antibody responses in humans, particularly in mucosal tissues, remain poorly understood. We used flow cytometry and single-cell sequencing to study S. pyogenes glycan (GAC) and protein (SpyCEP)-specific B cells in adult blood, spleen, tonsils, and human challenge cohorts. Our findings show that age and infection shift GAC and SpyCEP-specific B cell responses from IgM to IgG and IgA isotypes. Contrary to existing beliefs, glycan-specific B cells showed germinal center (GC) passage, typically seen only for protein antigens. GAC and SpyCEP-specific B cell receptors underwent mutation, clonally expansions and affinity maturation within the GC. However, GAC-specific cells expressed a unique transcriptional signature consistent with reduced ability to recruit or receive T cell help, resulting in fewer antibody-secreting cells. These insights reveal how multiple S. pyogenes encounters shape the quantity, quality and durability of B cell responses in systemic circulation and mucosal tissues. Our findings have broader implications for understanding anti-carbohydrate antibody responses to pathogens, while also illuminating how the memory responses recalled by vaccination differ dramatically between children and adults.