title: Stimulation of the B cell receptor, CD86 (B7-2), and the beta 2-adrenergic receptor intrinsically modulates the level of IgG1 and IgE produced per B cell.
abstract: Our findings using B cells from either wild-type, CD86-deficient, or beta 2-adrenergic receptor (beta2AR)-deficient mice suggest three mechanisms by which the level of IgG1 and IgE production can be increased on a per cell basis. Trinitrophenyl-specific B cells enriched from unimmunized mouse spleens were pre-exposed to Ag and/or the beta 2AR ligand terbutaline for 24 h before being activated by either a beta 2AR-negative Th2 cell clone or CD40 ligand/Sf9 cells and IL-4 in the presence or absence of an anti-CD86 Ab. Data suggest that the first mechanism involves a B cell receptor (BCR)-dependent up-regulation of CD86 expression that, when CD86 is stimulated, increases the amount of IgG1 and IgE produced in comparison to unstimulated cells. The second mechanism involves a BCR- and beta 2AR-dependent up-regulation of CD86 to a level higher than that induced by stimulation of either receptor alone that, when CD86 is stimulated, further increases the amount of IgG1 and IgE produced. The third mechanism is BCR-independent and involves a beta 2AR-dependent increase in the ability of a B cell to respond to IL-4. Flow cytometric and limiting dilution analyses suggest that the increase in IgG1 and IgE occurs independently from the isotype switching event. These findings suggest that the BCR, the beta 2AR, and CD86 are involved in regulating IL-4-dependent IgG1 and IgE production.
authors.affiliation: Departments of Microbiology and Immunology, and Cell Biology, Neurobiology and Anatomy, Loyola University Medical Center, Maywood, IL 60153, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Kasprowicz
authors.forename: A P
authors.initials: AP
authors.lastname: Kohm
authors.forename: M T
authors.initials: MT
authors.lastname: Berton
authors.forename: A J
authors.initials: AJ
authors.lastname: Chruscinski
authors.forename: A
authors.initials: A
authors.lastname: Sharpe
authors.forename: V M
authors.initials: VM
authors.lastname: Sanders
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists; D000818:Animals; D000941:Antigens / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand; D002478:Cells, Cultured; D005260:Female; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000494:pharmacology; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016012:Poisson Distribution; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism* / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D013726:Terbutaline / Q000494:pharmacology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000941:Antigens; D015703:Antigens, CD; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D007074:Immunoglobulin G; D008024:Ligands; D008562:Membrane Glycoproteins; D018343:Receptors, Adrenergic, beta-2; D011947:Receptors, Antigen, B-Cell; D023201:CD40 Ligand; D015847:Interleukin-4; D007073:Immunoglobulin E; D013726:Terbutaline