Reduced secreted mu mRNA synthesis in selective IgM deficiency of Bloom's syndrome.
Serum IgM concentrations were low although serum IgG and IgA concentrations were normal in both our patients with Bloom's syndrome. Although the percentages of surface IgM-bearing cells were not reduced, the numbers of IgM-secreting cells were markedly reduced. The membrane-bound mu (microns) and secreted mu (microseconds) mRNAs are produced from transcripts of a single immunoglobulin mu gene by alternative RNA processing pathways. The control of microseconds mRNA synthesis depends on the addition of poly(A) to microseconds C-terminal segment. In both patients, mu mRNA was well detected but microseconds C-terminal mRNA was scarcely detected, suggesting that microns mRNA was well transcribed but microseconds mRNA was not. There was, at least, no mutation or deletion in the microseconds C-terminal coding sequence, the RNA splice site (GG/TAAAC) at the 5' end of microseconds C-terminal segment and the AATAAA poly(A) signal sequence in both patients. Our results suggest that selective IgM deficiency in Bloom's syndrome is due to an abnormality in the maturation of surface IgM-bearing B cells into IgM-secreting cells and a failure of microseconds mRNA synthesis. Moreover, reduced microseconds mRNA synthesis may be due to the defect on developmental regulation of the site at which poly(A) is added to transcripts of the mu gene.
Kondo
N
N
Department of Paediatrics, Gifu University School of Medicine, Japan.
Ozawa
T
T
Kato
Y
Y
Motoyoshi
F
F
Kasahara
K
K
Kameyama
T
T
Orii
T
T
D000328:Adult; D001483:Base Sequence; D001816:Bloom Syndrome / Q000276:immunology*; D005260:Female; D005803:Genes, Immunoglobulin; D006801:Humans; D007075:Immunoglobulin M / Q000172:deficiency* / Q000235:genetics; D007136:Immunoglobulins / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis*
D007075:Immunoglobulin M; D007136:Immunoglobulins; D012333:RNA, Messenger