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.
Yoshimoto
T
T
Department of Immunology and Medical Zoology, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Japan.
Nagai
N
N
Ohkusu
K
K
Ueda
H
H
Okamura
H
H
Nakanishi
K
K
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