Enteroantigen-presenting B Cells Efficiently Stimulate CD4+ T Cells In Vitro

Background: Presentation of enterobacterial antigens by antigen-presenting cells and activation of enteroantigen-specific CD4(+) T cells are considered crucial steps in inflammatory bowel disease (IBD) pathology. The detrimental effects of such CD4(+) T cells have been thoroughly demonstrated in models of colitis. Also, we have previously established an in vitro assay where murine enteroantigen-specific colitogenic CD4(+)CD25(-) T cells are activated by splenocytes pulsed with an enterobacterial extract. Methods: CD4(+)CD25(-) T cells were stimulated in vitro with various kinds of enterobacterial extract-pulsed antigen-presenting cells. T-helper phenotypes were detected by flow cytometry. Results: We found that enteroantigen-pulsed splenic B cells possess a significantly higher and more sustained T cell stimulatory capacity than similarly pulsed splenic dendritic cells (DCs) measured by the level of enteroantigen-specific CD4(+)CD25(-) T cell proliferation. In support of this, we observed upregulation of classic maturation markers in B cells following incubation with enterobacterial antigens. Peritoneal and mesenteric lymph node-derived B cells were equally effective as enteroantigen-presenting stimulator cells. B cells greatly expanded the number of stimulated CD4(+) T cells, which acquired a T(H)2 phenotype. Interestingly, regulatory T cells were primarily activated by enteroantigen-pulsed B cells but not by similarly pulsed DCs. Conclusions: We conclude that B cells are superior stimulators of enteroantigen-specific CD4(+) T cells in vitro, favoring T(H)2 polarization. Thus, enteroantigen-processing and -presentation by B cells instead of by DCs might have opposing consequences for IBD development.