科研之友
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摘要
High and low serum concentrations of IgG3 are associated with the human G3 m(b) and G3 m(g) allotypes, respectively, We previously hypothesized that a low frequency of switching is the most likely defect in (g) allotype-positive individuals, and therefore analyzed the structure, recombination breakpoints, and binding of nuclear proteins to the switch (S)gamma 3 regions of these two allotypes. There are no allotype-associated differences in the length and basic structure of the S gamma 3, since both contain eighteen 79-bp repeats, However, we found a number of allotype-associated nucleotide changes, As in the mouse system, there is a preferential switching to the B site, or switch nuclear protein/nuclear factor-kappa B motif, with a clustering of switch breakpoints at the most 5' residue of the B site. The B site sequence used most frequently in switching was found to be mutated at this nucleotide in the (g) allotype-associated S gamma 3. This change was shown by electrophoretic mobility shift assay to alter the binding of the switch nuclear protein/nuclear factor-kappa B protein to the B site. Taken together, these data suggest that polymorphism within S gamma 3 may contribute to allotype-associated differences in IgG3 switching, and that specific sequences within the S gamma 3 79-bp repeats could be mechanistically important for switch recombination.
- 出版日期1997-6-15
