B7 costimulation in the development of lupus: autoimmunity arises either in the absence of B7.1/B7.2 or in the presence of anti-b7.1/B7.2 blocking antibodies.
Costimulatory molecules, termed B7.1 and B7.2, are present on the surfaces of APC and are important for the activation of T lymphocytes specific for both foreign Ags and autoantigens. We have examined the role of B7 costimulation in the MRL-lpr/lpr murine model of human systemic lupus erythematosus. MRL-lpr/lpr mice receiving both anti-B7.1 and anti-B7.2 Abs expressed significantly lower anti-small nuclear ribonucleoprotein particles (snRNP) and anti-dsDNA autoantibodies than did untreated mice. Anti-B7.2 Ab treatment alone inhibited anti-dsDNA autoantibody expression while having no effect on anti-snRNP autoantibody expression. Anti-B7.1 Ab treatment alone did not change the expression of either anti-snRNP or anti-dsDNA autoantibodies. Parallel studies performed in MRL-lpr/lpr mice genetically deficient in either B7.1 or B7.2 expressed autoantibody profiles comparable to those found in wild-type MRL-lpr/lpr mice. However, B7.1-deficient MRL-lpr/lpr mice exhibited distinct and more severe glomerulonephritis while B7.2-deficient MRL-lpr/lpr mice had significantly milder or absent kidney pathology as compared with age-matched wild-type mice. These studies indicate that each B7 costimulatory signal may control unique pathological events in murine systemic lupus erythematosus that may not always be apparent in autoantibody titers alone.
Liang
B
B
Department of Internal Medicine, Section of Rheumatology, Yale University School of Medicine, New Haven, CT 06510, USA.
Gee
R J
RJ
Kashgarian
M J
MJ
Sharpe
A H
AH
Mamula
M J
MJ
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D019138:Antibodies, Blocking / Q000096:biosynthesis / Q000502:physiology*; D000911:Antibodies, Monoclonal / Q000502:physiology; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis / Q000502:physiology*; D018122:B7-1 Antigen / Q000235:genetics* / Q000276:immunology*; D051940:B7-2 Antigen; D004247:DNA / Q000276:immunology; D005921:Glomerulonephritis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007668:Kidney / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology
D000974:Antibodies, Antinuclear; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001323:Autoantibodies; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins; D017411:Ribonucleoproteins, Small Nuclear; D004247:DNA