CD23-bound IgE augments and dominates recall responses through human naïve B cells (130.3)

Abstract

Abstract Peripheral blood human naïve B cells express high levels of CD23 and circulate pre-loaded with IgE. The antigen specificity of CD23-bound IgE presumably differs from the B cell receptor (BCR) and may reflect the antigen specific mix of free serum IgE. CD23-bound IgE is thought to enhance B cell antigen presentation raising the question of how a B cell might respond when presented with a variety of antigens and CD23-bound IgE specificities. We recently reported that an increase in CD23+ B cells is associated with resistance to schistosomiasis highlighting the potential importance of CD23-bound IgE in immunity. We sought to determine the relationship between BCR and CD23-bound IgE mediated B cell activation in schistosomiasis. Crude schistosome antigens downregulated basal B cell activation levels in individuals hyper-exposed to infectious worms. However, schistosome-specific IgE from resistant, occupationally exposed Kenyans recovered responses of naïve B cells to schistosome antigen. Furthermore, cross-linking of CD23 overrode intracellular signals mediated via the BCR illustrating its dominating role in B cell activation. Notably, the nature of the cognate antigen appeared to dictate the threshold of antigen-specific CD23-bound IgE required for B cell activation suggesting that CD23-bound IgE functions as a rheostat for B cell responses to antigenic stimuli. These results suggest that CD23-bound IgE augments and dominates host recall responses through naïve B cells.