Structural analysis of human γ3 intervening regions and switch regions: Implication for the low frequency of switching in IgG3‐deficient patients

摘要

AbstractHigh 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 Sγ3 and Iγ3, the switch frequency, switch breakpoints and the levels and initiation sites of Iγ3 transcripts both in normal blood donors expressing (b) or (g) allotypes as well as IgG3‐deficient (D) patients. A low switch frequency to γ3 was found in the (g) allotype IgG3D patients which may be caused in part by the allotype‐associated mutations in the Sγ3 region and in part by additional individual mutations observed in the A (SNAP) and B (SNIP/NF‐xB) sites in the Sγ3 repeat region. A higher Iγ3 germ‐line (GL) transcriptional rate was seen in cells from the IgG3D patient, suggesting that low levels of GL Iγ3 transcripts are not a major contributing factor to the defect. However, individual mutations in the Iγ3 region and differential splicing of GL Iγ3 transcripts were found which may affect the