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 gemline Cϵ transcripts and induced the productionof mature CϵmKNA. These effects were dependent on the presence of IL-4. Nested primer PCK revealed ddetional switch recombination occurring only in B ceils stimulated with both Ib4 and anti-CD40 mAb. DNA sequence analysis of switch fragments showed direct Sμ/Sϵ joining, without the deletions or duplications within Sμ often found in B ceils stimulated with IL-4 and Epstdn-Barrvirus. Analysis of the switch junction map sites showed “hot spots” for recombination within Sμ, but notwithin Sϵ. These findings indicate that ID4 provides a signal to B cells to induce germline Cϵ transcription and concurrent CD40 engagement induces Sμ/Sϵ deletional switch recombination, production of mature CϵmRNA, and IgE synthesis.
ASJC Scopus subject areas
- Immunology and Allergy