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 CE transcripts and induced the production of mature C-epsilon-mRNA. These effects were dependent on the presence of IL-4. Nested primer PCP 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 S-mu/SE joining, without the deletions or duplications within S-mu 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 S-mu, but not within S-epsilon. These findings indicate that IL-4 provides a signal to B cells to induce germline CE transcription and concurrent CD40 engagement induces S-mu/S-epsilon-deletional switch recombination, production of mature C-epsilon-mRNA, and IgE synthesis.