Germline transcripts of the murine immunoglobulin gamma 2a gene: structure and induction by IFN-gamma.

The switch in expression by B cells from IgM to IgG, IgE, or IgA is accomplished by a DNA deletion. The deletion event is regulated, in that specific cytokines direct the B cell to switch to one, or sometimes two, of the six possible murine heavy chain genes. Prior to switch recombination, cytokine treatment also induces the transcription of the constant, switch, and upstream regions of the targeted heavy chain. Much evidence indicates that IFN-gamma directs switch recombination to the murine gamma 2a gene. By developing probes specific for the gamma 2a gene, we demonstrate that IFN-gamma increases germline transcription of this gene in both normal B cells and in the 18.81.A20 pre-B lymphoma. We have obtained cloned copies of three different germline gamma 2a transcripts, each with a different donor splice site. We have also located the 5' ends of these transcripts. The vast majority of the germline gamma 2a transcripts have a long first exon (> 700 bp), consistent with observations by Severinson and her colleagues.