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

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Abstract
During B lymphocyte differentiation, inmmoglobulin heavy chain constant region (CH) genes undergo a unique series of DNA recombination events culminating in the CH class switch. CH switch (S) regions are located 2 kb 5′ of each CH gene except δ (i.e. μ, γ3, γl, γ2b, γ2a, ɛ and α). We describe the structural features of the γ3 switch region. Hybridization experiments show that Sγ3 has remarkable homology to both Sμ and other Sγ regions while Sμ possesses limited homology to the other Sγ sequences. However, Sμ possesses extensive sequence homology with Sɛ and Sα. The nucleotide sequence of Sγ3 reveals higher densities of Sμ repetitive sequences (GAGCT and GGGGT) and another S region cammon sequence (YAGGTTG) than observed for Sγ1 , Sγ2b or Sγ2a. In addition, the conservation of Sμ like repetitive sequences in Sγ regions is correlated with the 543′ → 3′ γ gene order (i.e. Sγ3>Sγ1>Sγ2b>Sγ2a). A model is presented which suggests that the unique features of Sγ3 may allow for successive switches from Cμ to any Cγ gene.