B7 costimulation and autoantigen specificity enable B cells to activate autoreactive T cells.
This study examines the role of B cells as auto-APCs in activating autoimmune T cells responses. Mice immunized with their own cytochrome c (cyt c) elicit no detectable B or T cell responses. However, mice first primed with a cryptic self peptide, mouse cyt c 81-104, followed at 3 wk with a boost of whole cyt c, elicit autoreactive T cells specific to self cyt c. T cell autoimmunity is not elicited in similarly immunized B cell-deficient (mu MT) mice. The expression of the B7-2 and/or B7-1 costimulatory molecules, as well as specificity to a self Ag, cyt c, enabled B cells to activate T cells to proliferate and to express IFN-gamma, IL-4, IL-5, and IL-10 cytokine mRNAs. In contrast, neither adoptively transferred B7- B cells nor nonspecific B7+ B cells were able to activate naive T cells. Moreover, anti-B7-2 treatment of mice prevented the in vivo expression of the IL-4, IL-5, and IFN-gamma cytokine mRNA responses. Our results suggest a major role of autoantigen-specific, B7-bearing B cells in breaking T cell tolerance to self Ag.
Roth
R
R
Department of Medicine, Yale University School of Medicine, New Haven, CT 06520-8031, USA.
Nakamura
T
T
Mamula
M J
MJ
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017951:Antigen Presentation; D015703:Antigens, CD / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D018122:B7-1 Antigen / Q000276:immunology*; D051940:B7-2 Antigen; D001483:Base Sequence; D002465:Cell Movement; D003574:Cytochrome c Group / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D007114:Immunization; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017634:Self Tolerance; D015398:Signal Transduction / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001324:Autoantigens; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; C497966:Cd86 protein, rat; D003574:Cytochrome c Group; D016207:Cytokines; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D012333:RNA, Messenger