Structural analysis of the murine IgG3 constant region gene.

We have determined the complete sequence of the gamma 3 heavy chain constant (C gamma 3) region gene of the BALB/c mouse including the 5'-flanking region up to the switch site and the 3'-flanking region past the end of the membrane exons. The C gamma 3 coding region, typical of other IgGs, is divided into six exons corresponding to the protein domains (C gamma (3)1, hinge, C gamma (3)2, and C gamma (3)3) and to the membrane carboxyl terminus (M1 and M2). The predicted amino acid sequence of the gamma 3 chain has three potential N-linked carbohydrate addition sites (including one in the membrane spacer segment), as compared with a single occurrence in the other mouse IgGs. Between the switch recombination region and the body of the C gamma 3 gene, there is a remarkable homology with a sequence between C mu and C delta which provides a rationale for an alternative, T cell-independent class-switch mechanism. We have used a computer to analyze the secondary structure of the gamma 3 mRNA precursor for the membrane form. We predict that this RNA precursor (approximately 12 000 bp) folds into four leaf-like domains which correspond to the variable region, the large IVS, the body of the constant region, and the membrane exons. This organization may have a role to play in the function of the mRNA precursor.