Deletional switch recombination occurs in interleukin-4-induced isotype switching to IgE expression by human B cells

There is controversy as to whether deletional rearrangement occurs between the IgM and IgE switch regions (S_μ, and S_ε, respectively) during switching to the IgE isotype. We have addressed the issue by stimulating normal human B cells, sorted for lack of expression of surface IgE, to produce IgE by infection with Epstein-Barr virus (EB V) in the presence of interleukin 4 (IL-4). Genomic DNA was amplified for S_μ/S_ε switch junction fragments by utilizing the nested-primer polymerase chain reaction. Switch junction fragments were amplified from B cells infected with EBV in the presence of IL-4 but not from B cells infected with EBV alone. The DNA sequence of these "switch fragments" revealed direct joining of S_μ to S_ε in each case. The recombination sites within S_μ were clustered within 900 base pairs at the 5′ end of the switch region, suggesting that there are "hot spots" for recombination within S_μ. The S_ε recombination sites were scattered throughout the S_ε region. These findings indicate that IL-4-induced isotype switching to IgE production in human B cells is accompanied by DNA rearrangements with joining of S_μ to S_ε.