Mouse C_μ 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 (C_μ)^1,2. The C_μ 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 (μ_m) and as soluble serum protein in IgM molecules into the blood (μ_s). Second, the C_μ region in μ_s is composed of four homology units or domains (C_μ1, C_μ2, C_μ3 and C_μ4) of approximately 110 amino acid residues plus a C-terminal tail of 19 residues^3,4. We asked two questions concerning the organisation of the C_μ gene segment. (1) Are the homology units separated by intervening DNA sequences as has been reported for α (ref. 5), γ₁ (ref. 6) and γ_2b (ref. 7) heavy chain genes? (2) Is the C-terminal tail separated from the C_μ4 domain by an intervening DNA sequence? If so, DNA rearrangements or RNA splicing could generate hydrophilic and hydrophobic C-terminal tails for the μ_s and μ_m polypeptides, respectively. We demonstrate here that intervening DNA sequences separate each of the four coding regions for C_μ domains, and that the coding regions for the C_μ4 domain and the C-terminal tail are directly contiguous.