CD40 ligand expressed on B cells in the BXSB mouse model of systemic lupus erythematosus.
Male BXSB mice, unlike female BXSB, develop a severe early onset lupus-like disease that has been linked to an intrinsic B cell defect. In investigating this B cell defect the present study showed that male, but not female, BXSB contained a higher percentage of large, activated splenic B cells that were more responsive to anti-CD40 mAb-induced proliferation. The hyperactivity of the large B cells from the male mice was also observed in the absence of anti-CD40 mAb or any other stimuli. In examining the mechanism of the B cell hyperactivity, it was found that 20% of unstimulated large B cells from male mice, unlike large B cells from female mice, expressed CD40 ligand (CD40L), a molecule normally expressed on activated CD4+ cells. The percentage of large B cells from the male BXSB that expressed CD40L was increased to 43% by stimulation with LPS. A functional role for CD40L expression on B cells was confirmed by showing that CD40-Ig blocked the spontaneous proliferation of the large B cells from male mice. In addition, the stimulatory capacity of the large B cells from the male mice was demonstrated by their ability to induce DNA synthesis in small B cells in a CD40L-dependent manner. These results demonstrated that large B cells from male BXSB expressed functionally active CD40L. It is likely that the B cell CD40L expression and increased susceptibility to CD40 signaling due to an intrinsic B cell hyperactivity promotes autoimmune disease in BXSB mice.
Blossom
S
S
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
Chu
E B
EB
Weigle
W O
WO
Gilbert
K M
KM
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D023201:CD40 Ligand; D004195:Disease Models, Animal; D005260:Female; D008024:Ligands; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D015398:Signal Transduction / Q000276:immunology*
D019013:CD40 Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D023201:CD40 Ligand