title: Lipopolysaccharide-activated B cells down-regulate Th1 immunity and prevent autoimmune diabetes in nonobese diabetic mice.
abstract: B cells can serve dual roles in modulating T cell immunity through their potent capacity to present Ag and induce regulatory tolerance. Although B cells are necessary components for the initiation of spontaneous T cell autoimmunity to beta cell Ags in nonobese diabetic (NOD) mice, the role of activated B cells in the autoimmune process is poorly understood. In this study, we show that LPS-activated B cells, but not control B cells, express Fas ligand and secrete TGF-beta. Coincubation of diabetogenic T cells with activated B cells in vitro leads to the apoptosis of both T and B lymphocytes. Transfusion of activated B cells, but not control B cells, into prediabetic NOD mice inhibited spontaneous Th1 autoimmunity, but did not promote Th2 responses to beta cell autoantigens. Furthermore, this treatment induced mononuclear cell apoptosis predominantly in the spleen and temporarily impaired the activity of APCs. Cotransfer of activated B cells with diabetogenic splenic T cells prevented the adoptive transfer of type I diabetes mellitus (T1DM) to NOD/scid mice. Importantly, whereas 90% of NOD mice treated with control B cells developed T1DM within 27 wk, <20% of the NOD mice treated with activated B cells became hyperglycemic up to 1 year of age. Our data suggest that activated B cells can down-regulate pathogenic Th1 immunity through triggering the apoptosis of Th1 cells and/or inhibition of APC activity by the secretion of TGF-beta. These findings provide new insights into T-B cell interactions and may aid in the design of new therapies for human T1DM.
authors: Department of Molecular and Medical Pharmacology, University of California School of Medicine, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA. jtian@mednet.ucla.edu
authors: J
authors: J
authors: Tian
authors: D
authors: D
authors: Zekzer
authors: L
authors: L
authors: Hanssen
authors: Y
authors: Y
authors: Lu
authors: A
authors: A
authors: Olcott
authors: D L
authors: DL
authors: Kaufman
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000473:pathology; D017209:Apoptosis / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002450:Cell Communication / Q000276:immunology; D002469:Cell Separation; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D015536:Down-Regulation / Q000276:immunology*; D053222:Fas Ligand Protein; D005260:Female; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000276:immunology*; D017710:Lymphocyte Transfusion; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011236:Prediabetic State / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
chemical_list: D001324:Autoantigens; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008024:Ligands; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016212:Transforming Growth Factor beta; D019014:fas Receptor