Quantitative regulation of class switch recombination by switch region transcription

The isotype specificity of immunoglobulin (Ig) class switching is regulated by a cytokine which induces transcription of a specific switch (S) region, giving rise to so-called germline transcripts. Although previous studies h ave demonstrated that germline transcription of an S region is required for class switch recombination (CSR) of that particular S region, it has not b een shown whether the level of S region transcription affects the efficienc y of CSR. We addressed this question by using an artificial DNA construct c ontaining a constitutively transcribed mu switch (S mu) region and an alpha switch (S alpha) region driven by a tetracycline-responsive promoter. The construct was introduced into a switch-inducible B lymphoma line and the qu antitative correlation between Sot region transcription and class switching efficiency was evaluated. The level of Su transcription was linearly corre lated with CSR efficiency, reaching a plateau at saturation. On the other h and, we failed to obtain the evidence to support involvement of either RNA- DNA heteroduplex or trans germline transcripts in CSR Taken together, it is likely that S region transcription and/or transcript processing in situ ma y be required for CSR. We propose that because of the unusual properties of S region DNA, transcription induces the DNA to transiently be single stran ded, permitting secondary structure(s) to form. Such structures may be reco gnition targets of a putative class switch recombinase.