The accelerated development of lupus-like autoimmune disease in male BXSB mice (H-2b, I-E-) is associated to the presence of a mutant gene, designated Yaa, located on their Y chromosome. To investigate whether the H-2b haplotype and/or the lack of expression of I-E molecules play any role in the Yaa-linked acceleration of autoimmune disease, an I-E+ BXSB.H-2d congenic strain was created by backcross procedures. We compared the development of autoimmune disease in the novel BXSB.H-2d (I-E+) strain to that of BXSB.H-2b (I-E-) and BXSB.H-2b/d (I-E+) heterozygous mice. Male BXSB.H-2d (I-E+) mice exhibited only a limited production of autoantibodies and a lower incidence of glomerulonephritis with a markedly prolonged survival rate, which were essentially identical to those of female BXSB mice of both-H-2b and H-2d haplotypes. However, BXSB.H-2b/d (I-E+) heterozygous males developed an accelerated disease comparable to that of conventional BXSB.H-2b (I-E-) male mice. These results indicate that the expression of I-E molecules and consequent clonal deletion or anergy of I-E reactive T cells does not appear to be responsible for the prevention of accelerated autoimmune disease in BXSB.H-2d (I-E+) male mice. The finding that the Yaa gene-induced acceleration of lupus-like autoimmune disease is modulated by gene(s) within or closely linked to the H-2 complex underlines the crucial role of the major histocompatibility complex and the polygenetic nature of autoimmune disease in BXSB mice.
SummaryThe accelerated autoimmune syndrome observed in BXSB/MpJ male mice is associated with the presence on the Y chromosome of an as yet unidentified mutant gene, designated Y chromosome-linked autoimmune accderation (~a). To study the mechanisms by which the Yaa gene accelerates and/or induces the production of autoantibodies, we have developed doublecongenic bone marrow chimeras containing B cells from autoimmune males carrying the Yaa gene, and from nonautoimmune male or female mice lacking it and differing by the Igh allotype. The analysis of the allotype of total immunoglobulins and anti-DNA antibodies in ~a + malenormal female (Yaa-) chimeric mice revealed that the selective activation of B ceils from autoimmune Yaa + male mice was responsible for the hypergammaglobulinemia and autoantibody production. This phenomenon was not due to an anti-HY interaction between female T helper cells and male B cells, because first, ~a + B cells were selectively stimulated to produce autoantibodies in ~a + male-Yaa-male chimeric mice; and second, normal male and female chimeras failed to develop an autoimmune syndrome. In addition, the fact that both B cell populations in ~a +-~a-chimeras similarly responded to a foreign antigen, human IgG, argues against the possibility that the selective activation of ~a + B cells may be due to their hyper-responsiveness to T helper signals. We propose that a cognate interaction of T helper cells with Yaa + B cells, because of possible T cell recognition of a ~a-related molecule expressed on ~a + B cells, may be responsible for the acceleration and/or induction of autoantibodies in BXSB/MpJ mice.
By the description of two cases of osteoarticular infections due to Kingella kingae in two young children we wish to draw the attention of clinicians to invasive infections due to this micro-organism. Since its biological characterization in 1976, K. kingae has been increasingly reported as a human pathogen. Most common presentations are endocarditis, bacteraemia, septic arthritis, osteomyelitis and spondylodiscitis. Interestingly, osteorticular involvement is largely predominant in previously healthy children. From the literature, we reviewed 51 cases of K. kingae bone and joint infections, representing 23 cases of septic arthritis, 17 of osteomyelitis and 11 spondylodiscitis. Of the cases 88% occurred in children below 5 years of age and in all cases only one bone or joint was involved. An underlying disorder could be found in only 4 patients. Since these infections have a favourable outcome with intravenous antibiotic treatment, proper isolation and identification of K. kingae is essential.
New Zealand Black (NZB) mice spontaneously develop an autoimmune hemolytic anemia together with a markedly increased production of polyclonal antibodies. The spontaneous generation of anti-mouse red blood cells (MRBC), anti-bromelain-treated MRBC (BrMRBC) and anti-DNA autoantibodies was compared to the polyclonal antibody formation in irradiated (800 rad) 2-month-old NZB mice reconstituted with bone marrow cells (BMC) from 2- or 10-month-old NZB mice. The injection of 10-month-old NZB BMC markedly accelerated the mortality rate in parallel with the progressive increase of anti-MRBC and anti-BrMRBC autoantibody production, but the spontaneous production of polyclonal IgM antibodies and anti-DNA autoantibodies was completely abolished down to the levels of non-autoimmune mice. In contrast, mice reconstituted with 2-month-old NZB BMC exhibited neither the acceleration of anemia nor the lack of polyclonal antibody production. These results strongly suggest that the spontaneous production of anti-MRBC autoantibodies, including anti-BrMRBC autoantibodies, in the NZB mouse occurs independently of the polyclonal B cell activation, and that they result from a specific immune stimulation, while the anti-DNA autoantibody production is a consequence of polyclonal antibody formation.
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