We have investigated the capacity of precursor B cells from normal (BDF₁) 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 εH chain gene transcription and to Sμ–Sε switch recombination. In differentiating precursor B cells from all three strains of mice, the development of similar numbers of CD19⁺, CD23⁺, CD40⁺, and MHC class II⁺ expressing B lineage cells and similar levels of εH chain gene transcription were induced. Efficient Sμ–Sε switching occurred in normal and RAG-2-deficient, but not in SCID, precursor B cells. Thus, the transcription of the εH chain is independent of the RAG-2 and the SCID gene product, while the Sμ–Sε switch recombination requires the SCID gene–encoded DNA-dependent protein kinase, but not the RAG-2 protein.