Structural analysis of human gamma 3 intervening regions and switch regions: implication for the low frequency of switching in IgG3-deficient patients.
High and low serum concentrations of IgG3 are associated with the human G3m(b) and G3m(g) allotypes, respectively. In the present study, we analyzed the structure of the S gamma 3 and I gamma 3, the switch frequency, switch breakpoints and the levels and initiation sites of I gamma 3 transcripts both in normal blood donors expressing (b) or (g) allotypes as well as IgG3-deficient (D) patients. A low switch frequency to gamma 3 was found in the (g) allotype IgG3D patients which may be caused in part by the allotype-associated mutations in the S gamma 3 region and in part by additional individual mutations observed in the A (SNAP) and B (SNIP/ NF-kappa B) sites in the S gamma 3 repeat region. A higher I gamma 3 germ-line (GL) transcriptional rate was seen in cells from the IgG3D patient, suggesting that low levels of GL I gamma 3 transcripts are not a major contributing factor to the defect. However, individual mutations in the I gamma 3 region and differential splicing of GL I gamma 3 transcripts were found which may affect the switching process.
Pan
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Division of Clinical Immunology, Karolinska Institute, Huddinge Hospital, Sweden.
Lindersson
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Y
Sideras
P
P
Hammarström
L
L
D001483:Base Sequence; D006801:Humans; D017099:IgG Deficiency / Q000097:blood / Q000235:genetics* / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000737:chemistry* / Q000235:genetics*; D007134:Immunoglobulin Switch Region / Q000276:immunology*; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D007438:Introns / Q000276:immunology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000276:immunology; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic / Q000276:immunology
D007074:Immunoglobulin G; D007148:Immunoglobulin mu-Chains