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 mu and S epsilon, 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 (EBV) in the presence of interleukin 4 (IL-4). Genomic DNA was amplified for S mu/S epsilon 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 mu to S epsilon in each case. The recombination sites within S mu were clustered within 900 base pairs at the 5' end of the switch region, suggesting that there are "hot spots" for recombination within S mu. The S epsilon recombination sites were scattered throughout the S epsilon 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 mu to S epsilon.
Shapira
S K
SK
Division of Allergy and Immunology, Children's Hospital, Boston, MA.
Jabara
H H
HH
Thienes
C P
CP
Ahern
D J
DJ
Vercelli
D
D
Gould
H J
HJ
Geha
R S
RS
D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D001483:Base Sequence; D015139:Blotting, Southern; D002460:Cell Line; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D005803:Genes, Immunoglobulin / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000235:genetics*; D007132:Immunoglobulin Isotypes / Q000235:genetics*; D007134:Immunoglobulin Switch Region / Q000235:genetics*; D015847:Interleukin-4 / Q000494:pharmacology*; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction / Q000379:methods; D011995:Recombination, Genetic; D015183:Restriction Mapping
D007132:Immunoglobulin Isotypes; D015345:Oligonucleotide Probes; D015847:Interleukin-4; D007073:Immunoglobulin E; D004247:DNA