THE SCID BUT NOT THE RAG-2 GENE-PRODUCT IS REQUIRED FOR S-MU-S-EPSILON HEAVY-CHAIN CLASS SWITCHING

We have investigated the capacity of precursor B cells from normal (BD F1) and V(D)J recombinase-deficient (RAG-2T) or defective (SCID) mice to be induced by a CD40-specific monoclonal antibody and IL-4 to epsil on H chain gene transcription and to S mu-S epsilon switch recombinati on. In differentiating precursor B cells from all three strains of mic e, the development of similar numbers of CD19(+), CD23(+), CD40(+), an d MHC class II+ expressing B lineage cells and similar levels of epsil on H chain gene transcription were induced. Efficient S mu-S epsilon s witching occurred in normal and RAG-2-deficient, but not in SCID, prec ursor B cells. Thus, the transcription of the epsilon H chain is indep endent of the RAG-2 and the SCID gene product, while the S mu-S epsilo n switch recombination requires the SCID gene-encoded DNA-dependent pr otein kinase, but not the RAG-2 protein.