title: Mice with the xid B cell defect are less susceptible to developing Staphylococcus aureus-induced arthritis.
abstract: To investigate the role of B cells in the development of experimental Staphylococcus aureus-induced arthritis, we used X-linked immunodeficiency (xid) mice that carry a Bruton's tyrosine kinase mutation affecting the function of B cells. NFR/N.xid and congenic NFR/N mice were inoculated i.v. with a toxic syndrome toxin-1 producing S. aureus LS-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, indicating that NFR/N.xid mice had significantly lower (p < 0.01) erosivity of the disease. Interestingly, infected NFR/N.xid mice showed decreased bacterial burden in blood, joints, and other organs compared with the control mice. Serologic studies displayed poor B cell responses to staphylococcal cell walls, toxic shock syndrome toxin-1, and ssDNA, accompanied by a low level of Igs in infected NFR/N.xid mice. More importantly, xid defect affected cytokine profile. The in vitro experiments showed that the lymphocytes from NFR/N.xid mice had low IL-6, but high IFN-gamma production upon stimulation with staphylococcal cell walls compared with NFR/N mice. Furthermore, the in situ hybridization technique revealed the relative increase of IFN-gamma, but marked decrease 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 expression was found between both strains. Our findings demonstrate that B cells may, directly or indirectly, contribute to the pathogenesis of septic arthritis. The results indicate that increased IFN-gamma production along with low IL-6 and IL-1 beta synthesis found in xid mice may provide a more favorable outcome of S. aureus arthritis.
authors.affiliation: Department of Clinical Immunology, University of Göteborg, Sweden.
authors.forename: Y X
authors.initials: YX
authors.lastname: Zhao
authors.forename: A
authors.initials: A
authors.lastname: Abdelnour
authors.forename: R
authors.initials: R
authors.lastname: Holmdahl
authors.forename: A
authors.initials: A
authors.lastname: Tarkowski
mesh_terms: D000818:Animals; D001170:Arthritis, Infectious / Q000276:immunology*; D001402:B-Lymphocytes / Q000502:physiology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D008040:Genetic Linkage; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D007371:Interferon-gamma / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D013203:Staphylococcal Infections / Q000276:immunology*; D014960:X Chromosome
chemical_list: D016207:Cytokines; D007371:Interferon-gamma