Regulation of C gamma 3 expression. Role of switch in the allotype-associated variation of human serum IgG3 levels

Abstract

Serum IgG3 levels are associated with G3m allotypes in humans. However, the molecular basis of this association has not been understood. In this study we have analyzed the biologic half-life, the secretion, the cell surface expression, the cytoplasmic content, and the mRNA expression of different allotypes. The biologic properties of the allotypes did not differ. However, the frequency of cells with membrane IgG3, cytoplasmic IgG3, and C gamma 3 mRNA was decreased in donors with a low serum IgG3, whereas the level of C gamma 3 mRNA expression in individual cells did not differ among cells of the different allotypes. As these findings indicated a pretranscriptional control of C gamma 3 expression, genomic DNA from donors with different allotypes were also studied. Despite the absence of gross, allotype-related differences in the I gamma 3 regions, we favor an upstream cis-element influencing C gamma 3 switching as the most likely explanation for variations in IgG3 serum levels.