title: Augmentation of antigen receptor-mediated responses by histamine H1 receptor signaling.
abstract: Histamine is considered one of the important mediators of immediate hypersensitivity and inflammation, and acts via G protein-coupled receptors. Here, we report that histamine may affect antigen receptor-mediated immune responses of T and B cells via a signal(s) from histamine H1 receptors (H1Rs). Histamine exhibited enhancing effects on the in vitro proliferative responses of anti-CD3epsilon- or anti-IgM-stimulated spleen T and B cells, respectively, at the culture condition that the fetal calf serum was dialyzed before culture and c-kit-positive cells were depleted from the spleen cells. In studies of histamine H1R knockout mice, H1R-deficient T cells had low proliferative responses to anti-CD3epsilon cross-linking or antigen stimulation in vitro. B cells from H1R-deficient mice were also affected, demonstrating low proliferative responses to B cell receptor cross-linking. Antibody production against trinitrophenyl-Ficoll was reduced in H1R-deficient mice. Other aspects of T and B cell function were normal in the H1R knockout mice. H1R-deficient T and B cells showed normal responses upon stimulation with interleukin (IL)-2, IL-4, CD40 ligand, CD40 ligand plus IL-4, and lipopolysaccharide. Collectively, these results imply that the signal generated by histamine through H1R augments antigen receptor-mediated immune responses, suggesting cross-talk between G protein-coupled receptors and antigen receptor-mediated signaling.
authors.affiliation: Department of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Banu
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000494:pharmacology; D001202:Ascitic Fluid / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D023201:CD40 Ligand; D002478:Cells, Cultured; D005362:Ficoll / Q000031:analogs & derivatives / Q000276:immunology; D019204:GTP-Binding Proteins / Q000502:physiology; D006160:Guanosine Triphosphate / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D007075:Immunoglobulin M / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016853:Muromonab-CD3 / Q000276:immunology / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011969:Receptors, Histamine H1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D014301:Trinitrobenzenes / Q000276:immunology; D051746:ZAP-70 Protein-Tyrosine Kinase