Interleukin-10 mediated autoregulation of murine B-1 B-cells and its role in Borrelia hermsii infection.
B cells are typically characterized as positive regulators of the immune response, primarily by producing antibodies. However, recent studies indicate that various subsets of B cells can perform regulatory functions mainly through IL-10 secretion. Here we discovered that peritoneal B-1 (B-1P) cells produce high levels of IL-10 upon stimulation with several Toll-like receptor (TLR) ligands. High levels of IL-10 suppressed B-1P cell proliferation and differentiation response to all TLR ligands studied in an autocrine manner in vitro and in vivo. IL-10 that accumulated in cultures inhibited B-1P cells at second and subsequent cell divisions mainly at the G1/S interphase. IL-10 inhibits TLR induced B-1P cell activation by blocking the classical NF-kappaB pathway. Co-stimulation with CD40 or BAFF abrogated the IL-10 inhibitory effect on B-1P cells during TLR stimulation. Finally, B-1P cells adoptively transferred from the peritoneal cavity of IL-10(-/-) mice showed better clearance of Borrelia hermsii than wild-type B-1P cells. This study described a novel autoregulatory property of B-1P cells mediated by B-1P cell derived IL-10, which may affect the function of B-1P cells in infection and autoimmunity.
Sindhava
Vishal
V
Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Kentucky, United States of America.
Woodman
Michael E
ME
Stevenson
Brian
B
Bondada
Subbarao
S
D000818:Animals; D053264:B-Cell Activating Factor / Q000494:pharmacology; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D015153:Blotting, Western; D001898:Borrelia / Q000276:immunology* / Q000472:pathogenicity; D019013:CD40 Antigens / Q000494:pharmacology; D049109:Cell Proliferation; D002478:Cells, Cultured; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015848:Interleukin-5 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000378:metabolism
D053264:B-Cell Activating Factor; D019013:CD40 Antigens; D015848:Interleukin-5; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D016753:Interleukin-10