B cells exposed to enterobacterial components suppress development of experimental colitis

• Published in: Inflammatory bowel diseases Vol. 18; no. 2; pp. 284 - 293
• Main Authors: Schmidt, Esben Gjerløff Wedebye, Larsen, Hjalte List, Kristensen, Nanna Ny, Poulsen, Steen Seier, Claesson, Mogens Helweg, Pedersen, Anders Elm
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.02.2012
• Subjects: Animals; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; B-Lymphocytes - microbiology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - microbiology; CD4-Positive T-Lymphocytes - transplantation; Colitis - immunology; Colitis - microbiology; colitis, IL‐10; Cytokines - biosynthesis; Cytokines - immunology; Enterobacter - chemistry; Enterobacter - immunology; enterobacteria; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Immune Tolerance; Interleukin-10 - biosynthesis; Interleukin-10 - genetics; Interleukin-10 - immunology; Mice; Mice, Inbred BALB C; Mice, Knockout; Mice, SCID; Regulatory B cells; Spleen - immunology; Spleen - metabolism; Spleen - microbiology; Spleen - secretion
• ISSN: 1078-0998; 1536-4844
• DOI: 10.1002/ibd.21769

Background: B cells positively contribute to immunity by antigen presentation to CD4+ T cells, cytokine production, and differentiation into antibody secreting plasma cells. Accumulating evidence implies that B cells also possess immunoregulatory functions closely linked to their capability of IL‐10 secretion. Methods: Colitis development was followed in CD4+CD25− T cell transplanted SCID mice co‐transferred with B cells exposed to an enterobacterial extract (ebx‐B cells). B and T cell cytokine expression was measured by flow cytometry and enzyme‐linked immunosorbent assay (ELISA). Results: We demonstrate that splenic B cells exposed to ebx produce large amounts of IL‐10 in vitro and express CD1d and CD5 previously known to be associated with regulatory B cells. In SCID mice transplanted with colitogenic CD4+CD25− T cells, co‐transfer of ebx‐B cells significantly suppressed development of colitis. Suppression was dependent on B cell‐derived IL‐10, as co‐transfer of IL‐10 knockout ebx‐B cells failed to suppress colitis. Ebx‐B cell‐mediated suppression of colitis was associated with a decrease in interferon gamma (IFN‐γ)‐producing TH1 cells and increased frequencies of Foxp3‐expressing T cells. Conclusions: These data demonstrate that splenic B cells exposed to enterobacterial components acquire immunosuppressive functions by which they can suppress development of experimental T cell‐mediated colitis in an IL‐10‐dependent way. (Inflamm Bowel Dis 2011;)