MICE WITH THE XID B-CELL DEFECT ARE LESS SUSCEPTIBLE TO DEVELOPING STAPHYLOCOCCUS AUREUS-INDUCED ARTHRITIS

To investigate the role of B cells in the development of experimental Staphylococcus aureus-induced arthritis, we used X-linked immunodefici ency (rid) mice that carry a Bruton's tyrosine kinase mutation affecti ng the function of B cells. NFR/N.xid and congenic NFR/N mice were ino culated i.v. with a toxic shock syndrome toxin-l producing S. aureus L S-1 strain. B cell-deficient NFR/N.xid mice developed less frequent(p < 0.01) and less severe(p < 0.01) arthritis than NFR/N mice did. These clinical findings were corroborated by histopathologic evaluation, in dicating that NFR/N.xid mice had significantly lower (p < 0.01) erosiv ity of the disease. Interestingly, infected NFR/N.xid mice showed decr eased bacterial burden in blood, joints, and other organs compared wit h the control mice. Serologic studies displayed poor B cell responses to staphylococcal cell walls, toxic shock syndrome toxin-, and ssDNA, accompanied by a low level of Igs in infected NFR/N.xid mice. More imp ortantly, rid defect affected cytokine profile. The in vitro experimen ts showed that the lymphocytes from NFR/N.xid mice had low IL-6, but h igh IFN-gamma production upon stimulation with staphylococcal cell wal ls compared with NFR/N mice. Furthermore, the in situ hybridization te chnique revealed the relative increase of IFN-gamma, but marked decrea se of IL-1 beta mRNA expression in spleens of infected NFR/N.xid mice. No significant difference in IL-4, IL-10, and TNF-alpha mRNA expressi on was found between both strains. Our findings demonstrate that B cel ls may, directly or indirectly, contribute to the pathogenesis of sept ic arthritis. The results indicate that increased IFN-gamma production along with low IL-6 and IL-1 beta synthesis found in rid mice may pro vide a more favorable outcome of S. aureus arthritis.