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.
Schmidt
Esben Gjerløff Wedebye
EG
Department of International Health, Immunology and Microbiology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. Esbens@sund.ku.dk
Kristensen
Nanna Ny
NN
Claesson
Mogens Helweg
MH
Pedersen
Anders Elm
AE
D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D003092:Colitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004755:Enterobacteriaceae / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D000942:Antigens, Bacterial; D016207:Cytokines