ABSTRACTResistance to schistosomiasis is associated with increased levels of serum parasite-specific IgE. IgE exerts its functions through its cellular receptors, FcεRI and FcεRII/CD23; however, its functional significance in humans requires further characterization. We previously reported that increased levels of CD23+B cells correlate with resistance to schistosomiasis in hyperexposed populations and sought to define their potential function and relationship with IgE. We found that CD23+B cells are a heterogeneous cell population with functional and phenotypic differences. Circulating CD23+B cells are uniquely activated in schistosomiasis and express the CD23b isoform and CXCR5, the homing receptor for lymphoid follicles. High CXCR5 expression by CD23+B cells was associated with the capacity to home to the cognate ligand CXCL13. CD23-bound IgE cross-linking increased surface expression of CXCR5, suggesting that CD23+B cells home directly into the lymphoid follicles upon antigen capture. As human schistosomiasis is an intravascular parasitic infection associated with a high antigenic burden in the blood, circulating CD23+B cells may play a role in the capture and shuttling of antigens directly to splenic follicles, highlighting a new role for circulating B cells. This function likely plays an important role in the development of protective immunity to infection with schistosomes.