ABERRANT PATTERNS OF IMMUNOGLOBULIN LEVELS IN WISKOTT-ALDRICH SYNDROME

We have investigated IgM deficiency in Wiskott-Aldrich syndrome patients. From the assessment of T and B cell functions in pokeweed mitogen-induced immunoglobulin (Ig) production, IgM deficiency was chiefly thought to result from B cell dysfunction. The percentages of surface IgM-bearing cells were decreased in peripheral blood mononuclear cells (PBMCs) and the number of IgM-secreting cells was also decreased. Lymphoblast cell lines (LCLs) from the patients have produced IgG and IgA, but never IgM. Moreover the expression of the C mu transcript from the patients' PBMCs and their LCLs were decreased, whereas the C gamma gene was well expressed. No germ-line polymorphism existed between the patients and the controls in the C mu region, and no mutation was detected in the mu s C-terminal and the M exon by nucleotide sequencing. These suggest that the Ig heavy chain (IGHC) isotype switch may be abnormally accelerated in the patients' B cells. While the methylation patterns of the human Ig enhancer gene region were the same between the patient and the control, the methylation patterns of the I gamma 1 region showed less methylation in the patient than in the control, which may cause low IgM expression and high expression levels of other classes located downstream of the IGHC gene.