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 beers linked to an intrinsic B cell defect. In investigating this B cell defect the present study showed that male, h ut not female, BXSB contained a higher percentage of large, activated splenic B cells that were more responsive to anti-CD40 mAb-induced pro liferation, The hyperactivity of the large cells from the male mice wa s also observed in the absence IPP 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 norm ally expressed on activated CD4(+) cells, The percentage of large Pt c ells from the male BXSB, that expressed CD40L was increased to 43% by stimulation with LPS. A functional role br CD40L expression on B cells was confirmed by showing that CD40-Ig blocked the spontaneous prolife ration of the la;ge B cells from male mice, In addition, the stimulato ry capacity of the large B cells from the male mice was demonstrated b y their ability to induce DNA synthesis in small B cells in a CD40L-de pendent manner. These results demonstrated that large B cells from mal e BXSB expressed functionally active CD40L. It is likely that the B ce ll CD40L expression and increased susceptibility to CD40 signaling due to an intrinsic B cell hyperactivity promotes autoimmune disease in B XSB mice.