Frequency analysis of functional Ig C epsilon gene expression in the presence and absence of interleukin 4 in lipopolysaccharide-reactive murine B cells from high and low IgE responder strains.
Nonresponder SJL mice produce low levels of antigen-specific IgE after immunization, compared to responder strains. Young athymic BALB/c nude mice are unable to produce antigen-specific or total IgE in their serum. These mice also have very numbers of background IgE-secreting cells in their lymphoid organs. High-responder BALB/c mice do have substantial numbers of background IgE-secreting cells while low-responder AKR mice show intermediate numbers. Similar differences were found when analyzing lipopolysaccharide (LPS)-reactive B cells in cell suspensions of spleen and bone marrow in limiting dilution cultures. Limiting dilution analysis of T cell-depleted splenic B cell cultures revealed that the defective IgE production in SJL mice is not due to an intrinsic B cell defect. This defect can be substantially overcome by addition of exogenous interleukin 4 (IL4) to these cultures. Furthermore, it was shown in limiting dilution cultures that SJL thymocyte feeder cells were able to suppress IgE production by LPS-activated high-responder BALB/c B cells. The addition of IL4 or neutralizing antibodies against IL4 or interferon-gamma to these cultures helped to overcome this suppressive effect to a large extent. We conclude that different IgE responder types are caused, at least in part, by a defective IL4 production or by a defect in the TH2 system that is functionally detectable at the level of thymocytes.
Savelkoul
H F
HF
Department of Cell Biology, Immunology and Genetics, Erasmus University, Rotterdem, The Netherlands.
Termeulen
J
J
Coffman
R L
RL
Van der Linde-Preesman
R A
RA
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D001854:Bone Marrow Cells; D002999:Clone Cells; D005786:Gene Expression Regulation; D005803:Genes, Immunoglobulin; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000235:genetics; D015847:Interleukin-4; D007378:Interleukins / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008815:Mice, Inbred Strains / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*
D007378:Interleukins; D008070:Lipopolysaccharides; D015847:Interleukin-4; D007073:Immunoglobulin E