Molecular analysis of the induction of immunoglobulin E synthesis in human B cells by interleukin 4 and engagement of CD40 antigen

The molecular events leading to immunoglobulin E (IgE) synthesis in human sIgE^- B cells stimulated with interleukin 4 (IL-4) and anti-CD40 monoclonal antibody (mAb) 626.1 were analyzed. Anti-CD40 mAb increased the levels of IL-4-induced germline C∈ transcripts and induced the production of mature C∈ mRNA. These effects were dependent on the presence of IL-4. Nested primer PCR revealed deletional switch recombination occurring only in B cells stimulated with both IL-4 and anti-CD40 mAb. DNA sequence analysis of switch fragments showed direct SμS∈ joining, without the deletions or duplications within Sμ often found in B cells stimulated with IL-4 and Epstein-Barr virus. Analysis of the switch junction map sites showed "hot spots" for recombination within Sμ, but not within S∈. These findings indicate that IL-4 provides a signal to B cells to induce germline C∈ transcription and concurrent CD40 engagement induces Sμ/S∈ deletional switch recombination, production of mature C∈ mRNA, and IgE synthesis.