LPS-stimulated SJL macrophages produce IL-12 and IL-18 that inhibit IgE production in vitro by induction of IFN-gamma production from CD3intIL-2R beta+ T cells.
SJL mice are known for their poor IgE production upon helminth infection. In this study, we have demonstrated that SJL standard B cells (85% IgM+ or B220+), prepared by complement-mediated T cell lysis, failed to proliferate and to produce IgE and IgG1 in response to LPS plus IL-4 in vitro. This diminished IgE production was restored by anti-IL-12 and enhanced by additional treatment with anti-IL-18, suggesting active suppression by the cells that produce IL-12 and IL-18. Indeed, SJL standard B cells were contaminated with Mac-1+ cells. Therefore, we removed macrophages by passing standard B cells through a Sephadex G-10 column (G10). Resultant cells (95% IgM+), designated as G10-B cells, responded to LPS and IL-4 by their proliferation and differentiation. G-10 treatment markedly diminished the proportion of B220- cells and Mac-1+ cells in SJL standard B cells. Furthermore, addition of SJL B220- cells dose dependently and MHC independently inhibited LPS plus IL-4-induced B cell growth and IgE production in SJL and BALB/c B cells. B220- cells in SJL standard B cells contained Mac-1+ cells (51%) and Fas ligand+ CD4-CD8- double-negative CD3intIL-2R beta+ T cells (26%). Thus, IL-12 and IL-18 produced by LPS-stimulated Mac-1+ cells stimulate this unique subpopulation of T cells to produce IFN-gamma, which in combination with Fas ligand, inhibits IgE production from the B cells. Our present results indicate that Mac-1+ cells and double-negative CD3intIL-2R beta+ T cells, uniquely abundant in the spleens of SJL mice, inhibit IgE production, indicating their new role in IgE response.
Department of Immunology and Medical Zoology, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Japan.
T
T
Yoshimoto
N
N
Nagai
K
K
Ohkusu
H
H
Ueda
H
H
Okamura
K
K
Nakanishi
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D002452:Cell Count; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology; D053222:Fas Ligand Protein; D005260:Female; D017099:IgG Deficiency / Q000276:immunology; D007106:Immune Sera / Q000494:pharmacology; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000172:deficiency; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology; D020382:Interleukin-18; D015847:Interleukin-4 / Q000494:pharmacology; D017493:Leukocyte Common Antigens / Q000235:genetics; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D019014:fas Receptor / Q000276:immunology
D000276:Adjuvants, Immunologic; D016207:Cytokines; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007106:Immune Sera; D007074:Immunoglobulin G; D020382:Interleukin-18; D008024:Ligands; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D019014:fas Receptor; D018664:Interleukin-12; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens