Mouse Cμ heavy chain immunoglobulin gene segment contains three intervening sequences separating domains

Abstract

The IgM molecule is composed of subunits made up of two light chain and two heavy chain (μ) polypeptides. The μ chain is encoded by several gene segments—variable (V), joining (J) and constant (Cμ)1,2. The Cμ gene segment is of particular interest for several reasons. First, the μ chain must exist in two very different environments—as an integral membrane protein in receptor IgM molecules (μm) and as soluble serum protein in IgM molecules into the blood (μs). Second, the Cμ region in μs is composed of four homology units or domains (Cμ1, Cμ2, Cμ3 and Cμ4) of approximately 110 amino acid residues plus a C-terminal tail of 19 residues3,4. We asked two questions concerning the organisation of the Cμ gene segment. (1) Are the homology units separated by intervening DNA sequences as has been reported for α (ref. 5), γ1 (ref. 6) and γ2b (ref. 7) heavy chain genes? (2) Is the C-terminal tail separated from the Cμ4 domain by an intervening DNA sequence? If so, DNA rearrangements or RNA splicing could generate hydrophilic and hydrophobic C-terminal tails for the μs and μm polypeptides, respectively. We demonstrate here that intervening DNA sequences separate each of the four coding regions for Cμ domains, and that the coding regions for the Cμ4 domain and the C-terminal tail are directly contiguous.