Independent regulation of DNA recombination and immunoglobulin (Ig) secretion during isotype switching to IgG1 and IgE.
Induction of switch recombination to the gamma 1 and epsilon immunoglobulin (Ig) heavy chain loci was examined in B cells preactivated with anti-Ig (B lymphoblasts). In B lymphoblasts cultured with interleukin 4 (IL-4), IL-5 induced the accumulation of S micro-S gamma 1 rearrangements, but not epsilon recombination. Thus, IL-5 facilitates switch recombination directed to the gamma 1 heavy chain locus by IL-4, but additional signals are required to drive rearrangements to epsilon. Lipopolysaccharide (LPS), in the presence of IL-4, induced the accumulation of both S micro-S gamma 1 and S micro-S epsilon rearrangements, and cells treated with LPS exhibited 40-50-fold more S micro-S gamma 1 rearrangements than cells cultured with IL-5. Induction of switch recombination was not always associated with secretion of the respective Ig isotype, since concentrations of IL-4 that were sufficient to direct switch recombination to gamma 1 and epsilon in blasts treated with LPS failed to elicit secretion of IgG1 and IgE. These results demonstrate differential requirements for switch recombination to the gamma 1 and epsilon loci, as well as independent regulation of Ig gene rearrangement and secretion of each isotype.
Purkerson
J M
JM
Searle Research and Development, Monsanto Company, St. Louis, Missouri 63198.
Isakson
P C
PC
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D001483:Base Sequence; D002478:Cells, Cultured; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism; D017931:DNA Primers; D005260:Female; D005786:Gene Expression Regulation; D005803:Genes, Immunoglobulin; D005812:Genes, Switch; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000235:genetics*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification / Q000235:genetics*; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis / Q000235:genetics*; D015847:Interleukin-4 / Q000494:pharmacology; D015848:Interleukin-5 / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D015183:Restriction Mapping; D013154:Spleen / Q000276:immunology
D017931:DNA Primers; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D015848:Interleukin-5; D015847:Interleukin-4; D007073:Immunoglobulin E; D004247:DNA