CD23-Bound IgE Augments and Dominates Recall Responses through Human Naive B Cells

Abstract

Human peripheral blood BCRμ+ B cells express high levels of CD23 and circulate preloaded with IgE. The Ag specificity of CD23-bound IgE presumably differs from the BCR and likely reflects the Ag-specific mix of free serum IgE. CD23-bound IgE is thought to enhance B cell Ag presentation to T cells raising the question of how a B cell might respond when presented with a broad mix of Ags and CD23-bound IgE specificities. We recently reported that an increase in CD23+ B cells is associated with the development of resistance to schistosomiasis, highlighting the potential importance of CD23-bound IgE in mediating immunity. We sought to determine the relationship between BCR and CD23-bound IgE-mediated B cell activation in the context of schistosomiasis. We found that crude schistosome Ags downregulate basal B cell activation levels in individuals hyperexposed to infectious worms. Schistosome-specific IgE from resistant, occupationally exposed Kenyans recovered responses of B cells to schistosome Ag. Furthermore, cross-linking of CD23 overrode intracellular signals mediated via the BCR, illustrating its critical and dominating role in B cell activation. These results suggest that CD23-bound IgE augments and dominates recall responses through naive B cells.

CD23b Isoform Expression in Human Schistosomiasis Identifies a Novel Subset of Activated B Cells

“…We reported that CD23 cross-linking is an important mediator in B cell signaling, particularly of Syk activation (21). Besides the role that CD23-bound IgE plays, B cells have been shown to transport immune complexes to follicular dendritic cells (FDC) in the GC in a CD21-dependent manner (12).…”

“…We demonstrated that CD23-bound, parasite-specific IgE induces kinase activation in B cells, but the role(s) of these signaling pathways in host resistance remains unclear (21). Indeed, the immunobiology of CD23 is highly complex.…”

“…The functional significance of IgE in humans requires further characterization, but the antibody may facilitate parasite attrition or immune responses (20,21). IgE exerts its functions through its cellular receptors, FcεRI and FcεRII/CD23, which are expressed by a variety of cells (19).…”

“…Tonsil and Ramos B cells were cultured overnight with 20 ng/ml of IL-4 to upregulate nascent surface CD23. The following day, B cells were subjected to an IgE-binding protocol to load nascent CD23 molecules with IgE (21). B cells were rotated in Tris-buffered saline (TBS) buffer containing 2 mM CaCl 2 with 20 g of 4-hydroxy-3-nitrophenylacetyl (NP)-specific IgE (AbD Serotec, Oxford, United Kingdom).…”

“…CD23 activation was assessed by phosphokinase activity with Phospho-Flow. B cells were cultured in the presence of stimuli for 10 min, fixed with paraformaldehyde, and permeabilized with BD Phosflow Perm buffer II (21). Cells were vortexed, incubated with fluorescently labeled anti-phospho-Syk (pY352) or -ZAP70 (Y319) (BD Pharmingen) at room temperature for 30 min in the dark, washed, and evaluated by flow cytometry.…”