| Research Abstract |
X-linked hyper-IgM syndrome is caused by the gene abnormality of CD154 (CD40 ligand) expressed on activated T cells. Some relationship between the nature of gene mutations and clinical severity was observed by the gene analysis of an amount of cases. B cells of female cases of this syndrome did not produce IgE even when stimulated with IL-4 and anti-CD40 antibody, which suggested the defect of CD40 signaling. In one female case, gene disruption of CD154 caused by chromosomal translocation was thought to be the pathogenesis. Concerned with CD40 signaling, it was disclosed that Ku molecule participating DNA repair was initially associated with CD40 and moved to the nucleus in B cells when B cells are activated by IL-4 and anti-CD40 stimulus. Development of B cells is impaired by the gene mutation of tyrosine kinase Btk in X-linked agammaglobulinemia. Small amount of remaining B cells did produce immunoglobulin by stimulation with IL-4 and anti-CD40, which indicated that Btk is essential for the development of B cells but not necessarily needed for B cell function. T cells from HLA class II deficiency did not express CD154 by first activation with mitogen but did by second stimulation. This indicated T cells of the patients are retained in naive state and this may the cause of defective antibody production. Gene mutation of WASP is the pathogenesis of Wiskott-Aldrich syndrome. By the transfection experiment of WASP gene, it was proved that WASP is essential for actin polymerization in the cells, and it also associates with Grb2, Btk and PIP2 which are concerned in signal transduction. Defect of these function is thought to be related with thrombocyto- penia and T cell deficiency. Mild mutation seemed to cause only thrombocytopenia and megakaryocyte colony was normally developed in these patients in in vitro experiment, which suggest defect is present not in megakaryocyte development but in thrombopoiesis.
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