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

Abstract

Resistance to schistosomiasis is associated with increased levels of serum parasite-specific IgE. IgE exerts its functions through its cellular receptors, FcRI and FcRII/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.

Immuno-evasive tactics by schistosomes identify an effective allergy preventative

“…We also noted an increase in the 50–70kDa sCD23 in schistosome-treated supernatants (Fig. 2A; middle), although our previous results indicate that schistosomes do not increase mRNA of inducible CD23 (18). Both the 17- and 15kDa sCD23 fragments were identified in serum from individuals infected with schistosomes (Fig.…”

“…We next sought to reconcile our previously published findings demonstrating that schistosome antigens do not affect surface levels of CD23, including those on circulating B cells from schistosome hyper-exposed Kenyans (18). We hypothesized that this would be explained by the observation that peripheral blood CD23+ B cells are pre-loaded with bound IgE, which might block cleavage sites (17).…”

“…We recently reported that schistosome antigens did not alter the surface level of CD23 on B cells (18), but these experiments did not test whether there were changes to the soluble form of CD23. We thus measured levels of sCD23 in cell-free supernatants following treatment of B cells with schistosome antigens and found a modest increase (Fig.…”

“…We previously reported that an increase in circulating FcεRII/CD23 + B cells was associated with the development of resistance in schistosome hyper-exposed populations from Kenya (16). Our findings suggested that CD23+ B cells may utilize surface bound IgE to capture and shuttle antigens from the bloodstream to the splenic follicles to augment immune responses (17, 18). Thus, IgE likely has diverse and unexpected roles in human immunity that remain to be defined.…”

Role of Chemokines and Trafficking of Immune Cells in Parasitic Infections

“…Ligands for CXCR4, CXCR5, and CCR7 all cooperate to position B cells to mount appropriate antibody responses. High expression of CXCR5 in naïve B cells keeps them confined to the B cell follicles that are lined with CXCL13 [13, 90]. Upon activation with antigen, B cells upregulate CCR7 facilitating migration toward the T cell zone to receive T cell help [11, 12, 91].…”