Nucleotide sequence and properties of the murine γ3 immunoglobulin heavy chain gene switch region: Implications for successive C_γ gene switching

During B lymphocyte differentiation, inmmoglobulin heavy chain constant region (C_H) genes undergo a unique series of DNA recombination events culminating in the C_H class switch. C_H switch (S) regions are located 2 kb 5′ of each C_H gene except δ (i.e. μ, γ3, γl, γ2b, γ2a, e{open} and α). We describe the structural features of the γ3 switch region. Hybridization experiments show that S_γ3 has remarkable homology to both S_μ and other S_γ regions while S_μ possesses limited homology to the other S_γ sequences. However, S_μ possesses extensive sequence homology with S_e{open} and S_α. The nucleotide sequence of S_γ3 reveals higher densities of S_μ repetitive sequences (GAGCT and GGGGT) and another S region cammon sequence (YAGGTTG) than observed for S_γ1 , S_γ2b or S_γ2a. In addition, the conservation of S_μ like repetitive sequences in S_γ regions is correlated with the 543′ → 3′ γ gene order (i.e. S_γ3>S_γ1>S_γ2b>S_γ2a). A model is presented which suggests that the unique features of S_γ3 may allow for successive switches from C_μ to any C_γ gene.