title: Suppression of antigen-specific Th2 cell-dependent IgM and IgG1 production following norepinephrine depletion in vivo.
abstract: The mechanism by which the Th2 cell-dependent Ab response is modulated by the sympathetic neurotransmitter norepinephrine (NE) was investigated. Our model system used the severe combined immunodeficient (scid) mouse that was depleted of NE with 6-hydroxydopamine before reconstitution with a clone of beta2-adrenergic receptor (beta2AR)neg KLH-specific Th2 cells and resting trinitrophenyl (TNP)-specific beta2ARpos B cells enriched from the spleens of unimmunized mice. Following challenge with TNP-keyhole limpet hemocyanin (KLH), Ab production in these mice was hapten-, carrier-, and allotype-specific as well as MHC restricted. Depletion of NE resulted in a 50-75% suppression of the primary anti-TNP IgM response compared with that of NE-intact controls, while the secondary IgM response returned to control levels. In contrast, both the primary and secondary anti-TNP IgG1 responses were suppressed by 85 and 40%, respectively. Using NE-intact mice exposed to either a betaAR- or alphaAR-selective antagonist, the effect of NE on the Ab response was shown to be mediated by the betaAR. In addition, administration of a beta2AR-selective agonist to NE-depleted mice partially reversed the suppressed Ab response that resulted from NE depletion. Expression of the beta2AR on TNP-specific B cells was confirmed by radioligand binding, immunofluorescence, and cAMP analysis. Also, while splenic histology was comparable in NE-intact and NE-depleted mice before Ag exposure, follicle expansion and germinal center formation were suppressed in NE-depleted mice after Ag exposure. Taken together, these results suggest that NE stimulation of the beta2AR expressed on B cells is necessary for the maintenance of an optimal primary and secondary Th2 cell-dependent Ab response in vivo.
authors.affiliation: Department of Cell Biology, Loyola University Medical Center, Maywood, IL 60153, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Kohm
authors.forename: V M
authors.initials: VM
authors.lastname: Sanders
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000637:transplantation; D002999:Clone Cells / Q000637:transplantation; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006241:Haptens / Q000276:immunology; D006433:Hemocyanins / Q000276:immunology; D007108:Immune Tolerance / Q000235:genetics; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000097:blood; D007075:Immunoglobulin M / Q000096:biosynthesis* / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D009638:Norepinephrine / Q000235:genetics / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013563:Sympathectomy, Chemical; D018418:Th2 Cells / Q000276:immunology* / Q000637:transplantation; D014301:Trinitrobenzenes / Q000276:immunology
chemical_list: D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D006241:Haptens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011943:Receptors, Adrenergic, beta; D014301:Trinitrobenzenes; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; D009638:Norepinephrine