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We have demonstrated that CD45, a receptor-type protein tyrosine phosphatase, selectively regulates IgG production at the generative phase of precursors of IgG producers whereas Lyb-2 regulates IgG1 production induced by IL-4 in lipopolysaccharide (LPS)-activated B cells by acting on the generation of IgG1 precursor cells. These results point to an interesting possibility that both CD45 and Lyb-2 mediate a critical regulatory step(s) in IgG class switching. The present study was conducted to examine this possibility by elucidating the molecular mechanisms whereby CD45 and Lyb-2 control IgG synthesis in B cells activated by LPS and IL-4. Northern blot analysis showed that steady-state levels of C gamma 3, C gamma 2b and C gamma 1, but not Cmu, mRNA in LPS-activated B cells were reduced approximately 3- to 5-fold by CD45 mAb, and that the C gamma 1 mRNA level in B cells activated by LPS and IL-4 was significantly decreased by Lyb-2 mAb and CD45 mAb. Further, CD45 mAb inhibited expression of germline gamma 2b and gamma 3 transcripts induced by LPS and germline gamma 1 transcript expression induced by IL-4 plus LPS, but caused no inhibition in IL-4-induced germline gamma 1 transcript expression. In contrast, Lyb-2 mAb did not exert any inhibitory effect on the generation of germline gamma 1 transcripts induced by IL-4 and LPS or by IL-4 alone.(ABSTRACT TRUNCATED AT 250 WORDS)

A new HLA-D specificity was found in the Japanese population in two different laboratories. Japanese cell YT, found at Stanford, California, was A9,BW22J,CW1 and cell Wa, found at Sapporo, Japan, was A9,BW22J homozygous. They were shown to be HLA-D identical to the homozygous Japanese cell AH which submitted to the VIth International Histocompatibility Testing Workshop (Workshop number 2-001). This specificity was common in the Japanese (gf = 0.089) but completely absent from 62 Caucasians tested. Strong association of this specificity with HLA-BW22J was demonstrated.

One of the hallmarks of immunological abnormalities in mice that are prone to syndromes resembling systemic lupus erythematosus is polyclonal activation of B cells and a switch of serum immunoglobulins or autoantibodies from IgM to IgG that coincides with onset of autoimmune disease. Therefore, we investigated whether the development of autoimmunity can be alleviated in such mice by administration of monoclonal alloantibody directed against Ly-5, because this was known to reduce levels of polyclonal IgG antibody without affecting other immunoglobulin isotypes. Our results indicate that at least some forms of autoimmune disease may be effectively treated by thus reducing the concentration of IgG autoantibody in this manner.

One homozygous cell "Wa" for HLA-D alleles, associated with HLA-Bw22J (Japanese specific variant of HLA-Bw22), was found in a Japanese family. The HLA-D antigenic specificity defined by this cell has been tentatively named LD-Wa. Phenotype frequency of LD-Wa in the Japanese population was 0.16 (13/81). HLA-D typing for LD-Wa was performed in patients with the Vogt-Koyanagi-Harada syndrome (Harada's disease) with which Bw22J is strongly associated (15/35, 42.9%; corrected P less than 0.02). LD-Wa was presented in 22 of 33 patients (33.7%; P less than 0.0000003). The association of LD-Wa with Harada's disease was stronger than that of Bw22J, and this implies that there might be one of the disease susceptibility gene loci affecting the development of this disease more closely linked to an HLA-D gene locus than the HLA-B locus.

Four families in which asthma occurred in more than three members, and in which there were at least three children, were studied in terms of clinical symptoms, serum IgE levels determined by RIST and RAST, and HLA haplotypes. No association between clinical asthma and serum IgE level was found, but a close association between asthma and a particular HLA haplotype in a family was demonstrated. It was therefore postulated that a disease susceptibility gene closely linked to an HLA gene complex may play a role in the development of asthma.