Interleukin-12 and -10 and gamma interferon regulate polyclonal and ligand-specific expansion of murine B-1 cells.
B-1 cells (CD5+ B220+) are a self-replenishing lineage of B cells which are autoreactive and capable of producing large amounts of interleukin-10 (IL-10). In mice experimentally infected with the human helminth parasite Schistosoma mansoni, expansion of B-1 cells is seen in the peritoneal cavity just prior to egg laying. In naive mice, B-1 cell expansion can be elicited by intraperitoneal injection of saline soluble egg antigens (SEA) or the polylactosamine sugar lacto-N-fucopentaose III (LNFPIII), which contains the Lewis-X trisaccharide. In this study, we demonstrate that LNFPIII is the major stimulus in SEA responsible for expansion of B-1 cells, since SEA-induced B-1 outgrowth is blocked by multiple injections of non-cross-linked free LNFPIII. IL-10 is an autocrine growth factor for B-1 cells, and we show that B-1 outgrowth after SEA and LNFPIII administration is inhibited by injection of anti-IL-10 antibodies. Furthermore, SEA- and LNFPIII-induced expansion of B-1 cells is inhibited by in vivo administration of recombinant murine IL-12 or recombinant gamma interferon. These data suggest that activation and expansion of IL-10-producing B-1 cells are governed via cross-regulatory cytokines.
Department of Tropical Public Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
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Velupillai
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Sypek
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Harn
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D018956:CD5 Antigens / Q000032:analysis; D002999:Clone Cells; D016207:Cytokines / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000032:analysis; D008024:Ligands; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009844:Oligosaccharides / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012550:Schistosoma mansoni / Q000276:immunology*
D000947:Antigens, Helminth; D018956:CD5 Antigens; D016207:Cytokines; D008024:Ligands; D009844:Oligosaccharides; D011994:Recombinant Proteins; D016753:Interleukin-10; D018664:Interleukin-12; C045442:lacto-N-fucopentaose I; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens