Activated B cells express increased levels of costimulatory molecules in young autoimmune NZB and (NZB x NZW)F(1) mice.
Polyclonal B cell activation is a hallmark of autoimmune disease in NZB and (NZB x NZW)F(1) (NZB/W) mice. However, the mechanism by which this activated cell subset facilitates disease development is unknown. We recently showed that resting B cells from these mice demonstrate enhanced expression of costimulatory molecules in response to CD40 crosslinking (Jongstra-Bilen et al., J. Immunol. 159,5810-5820, 1997). This led us to question whether activated B cells expressed costimulatory molecules in vivo. Using flow cytometry we found that NZB and NZB/W mice have an increased proportion of splenic B cells expressing B7.1 and elevated levels of B7.2 and ICAM-1. These B cells isolate within the low-density activated population and possess the phenotypic characteristics of marginal zone B cells. The levels of B7.1 on the activated B cell population are similar to those induced by CD40 stimulation raising the possibility that activated B cells in NZB and NZB/W mice provide costimulatory signals to self-reactive T cells leading to loss of tolerance.
Wither
J E
JE
The Arthritis Centre of Excellence, The Toronto Hospital Research Institute, The Toronto Hospital-Western Division, Canada.
Roy
V
V
Brennan
L A
LA
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D000954:Antigens, Surface / Q000235:genetics; D001327:Autoimmune Diseases / Q000378:metabolism; D001402:B-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D018122:B7-1 Antigen / Q000378:metabolism*; D019013:CD40 Antigens / Q000096:biosynthesis; D023201:CD40 Ligand; D002499:Centrifugation, Density Gradient; D005260:Female; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008814:Mice, Inbred NZB / Q000276:immunology*; D010641:Phenotype; D011205:Povidone; D012822:Silicon Dioxide; D015854:Up-Regulation
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D018122:B7-1 Antigen; D019013:CD40 Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; C016039:Percoll; D012822:Silicon Dioxide; D011205:Povidone