title: B cells activated by lipopolysaccharide, but not by anti-Ig and anti-CD40 antibody, induce anergy in CD8+ T cells: role of TGF-beta 1.
abstract: B cells recognize Ag through their surface IgRs and present it in the context of MHC class II molecules to CD4(+) T cells. Recent evidence indicates that B cells also present exogenous Ags in the context of MHC class I to CD8(+) T cells and thus may play an important role in the modulation of CTL responses. However, in this regard, conflicting reports are available. One group of studies suggests that the interaction between B cells and CD8(+) T cells leads to the activation of the T cells, whereas other studies propose that it induces T cell tolerance. For discerning this dichotomy, we used B cells that were activated with either LPS or anti-Ig plus anti-CD40 Ab, which mimic the T-independent and T-dependent modes of B cell activation, respectively, to provide accessory signals to resting CD8(+) T cells. Our results show that, in comparison with anti-Ig plus anti-CD40 Ab-activated B cells, the LPS-activated B cells (LPS-B) failed to induce significant levels of proliferation, cytokine secretion, and cytotoxic ability of CD8(+) T cells. This hyporesponsiveness of CD8(+) T cells activated with LPS-B was significantly rescued by anti-TGF-beta1 Ab. Moreover, it was found that such hyporesponsive CD8(+) T cells activated with LPS-B had entered a state of anergy. Furthermore, LPS-B expresses a significantly higher level of TGF-beta1 on the surface, which caused the observed hyporesponsiveness of CD8(+) T cells. Therefore, this study, for the first time, provides a novel mechanism of B cell surface TGF-beta1-mediated hyporesponsiveness leading to anergy of CD8(+) T cells.
authors.affiliation: National Center for Cell Science, Pune, Maharashtra, India. School of Biotechnology, Devi Ahilya Vishwavidyalaya, Indore, Madhya Pradesh, India.
authors.forename: Vrajesh V
authors.initials: VV
authors.lastname: Parekh
authors.forename: Durbaka V R
authors.initials: DV
authors.lastname: Prasad
authors.forename: Pinaki P
authors.initials: PP
authors.lastname: Banerjee
authors.forename: Bimba N
authors.initials: BN
authors.lastname: Joshi
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.forename: Gyan C
authors.initials: GC
authors.lastname: Mishra
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology*; D015703:Antigens, CD / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000276:immunology*; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D007106:Immune Sera / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D007376:Interleukin-2 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000502:physiology*; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D016207:Cytokines; D007106:Immune Sera; D007376:Interleukin-2; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10