title: Induction of germinal centers by MMTV encoded superantigen on B cells.
abstract: It has not been established whether an endogenous superantigen (SAg) expressed on B cells can induce germinal centers (GCs). An interesting model is that of mammary tumor virus encoded viral SAgs, which induce vigorous T cell proliferation and are predominantly expressed on activated B cells. We have used this model to analyze the possibility that direct stimulation of Mtv7+ DBA/2 B cells by vSAg-responsive (Vbeta6+) BALB/c T cells can give rise to GCs. Injection of BALB/c SCID mice i.v. with 2 x 10(6) DBA/2 B cells, together with LPS, followed by 2 x 10(6) BALB/c T cells induces numerous large splenic GCs within 3-5 days. The GCs are still large on day 7, but are very much reduced by day 10. B cell activation with LPS is needed for this effect. These GCs form in spite of the apparent absence of follicular dendritic cells (FDCs) as judged by staining for several FDC surface markers. Control mice receiving either BALB/c T or DBA/2 B cells + LPS alone or DBA/2 T + B cells + LPS fail to exhibit any GCs on days 3-7. Numerous small clusters of PNA+ cells, but few large GCs are observed when TNF-R(p55)-Ig is also injected, whereas LTbetaR-Ig treatment impeded the formation of aggregations of these cells even further, leaving scattered PNA+ single cells and very small clumps throughout the white pulp of the spleens. Anti-TNFalpha had no effect. These results suggest that endogenous vSAg mediated GC formation is independent of antigen trapping by FDCs.
authors.affiliation: Department of Pathology and Comprehensive Kaplan Cancer Center, New York University School of Medicine, NY 10016, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Simmons
authors.forename: M
authors.initials: M
authors.lastname: Simms
authors.forename: R
authors.initials: R
authors.lastname: Chiarle
authors.forename: F
authors.initials: F
authors.lastname: Mackay
authors.forename: V K
authors.initials: VK
authors.lastname: Tsiagbe
authors.forename: J
authors.initials: J
authors.lastname: Browning
authors.forename: G
authors.initials: G
authors.lastname: Inghirami
authors.forename: G J
authors.initials: GJ
authors.lastname: Thorbecke
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000378:metabolism; D000956:Antigens, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D018858:Germinal Center / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008324:Mammary Tumor Virus, Mouse / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D016513:Mice, SCID; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000956:Antigens, Viral; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C095378:Mtv-7 superantigen, Mouse mammary tumor virus; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I