Frequency analysis of functional Ig Cεgene expression in the presence and absence of interleukin 4 in lipopolysaccharide‐reactive murine B cells from high and low IgE responder strains

摘要

AbstractNonresponder 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 low 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‐y 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 th