Transcriptional regulation of the germline immunoglobulin C_α and C_ε genes: Implications for commitment to an isotype switch

Lymphokine directed isotype switching is preceded by the induced expression of the corresponding germline Ig heavy chain constant region (C_H) gene. This association favors a model in which lymphokine induced germline CH gene expression promotes switch recombination by increasing the accessibility of the switch region to a recombinase(s). An important prediction of this model is that the induction of germline C_H RNAs represents increased specific de novo transcription. To test if this prediction is fulfilled by the switch commitment factors, IL-4 and transforming growth factor-β (TGF-β), we have utilized a B cell line, 1.29, that switches from IgM to IgE and IgA in vitro. In this cell line, IL-4 and TGF-β increase germline C_ε and C_α RNA levels respectively, predominantly by elevating transcription of these genes. Transcription of germline C_ε and C_α genes appears to be independently regulated and is not affected by lipopolysaccharide or IL-5. These results are discussed in the context of the molecular events necessary to commit a B cell to an isotype switch.