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.
Inoue
R
R
Department of Pediatrics, Gifu University School of Medicine, Japan.
Kondo
N
N
Kuwabara
N
N
Orii
T
T
D000293:Adolescent; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D002478:Cells, Cultured; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics / Q000276:immunology; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D007136:Immunoglobulins / Q000096:biosynthesis / Q000097:blood*; D008297:Male; D008969:Molecular Sequence Data; D011043:Pokeweed Mitogens / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D014923:Wiskott-Aldrich Syndrome / Q000276:immunology*
D007136:Immunoglobulins; D011043:Pokeweed Mitogens