IL-2 INHIBITS IL-4-DEPENDENT IGE AND IGG1 PRODUCTION IN-VITRO AND IN-VIVO

Nippostrongylus brasiliensis (Nb) infection of mice induces IL-4 produ cing CD4(+) T cells which stimulate polyclonal IgE and IgG1 production , providing a model system to study IL-4 action on a cells in vivo. B cell la expression and the proportion of IL-2R beta positive B cells w ere increased in Nb-inoculated mice, and B cells from these mice respo nded to IL-2 by prompt and marked cell growth. Injection of anti-IL-4 1 day after Nb inoculation substantially inhibited these responses, in dicating that they were largely IL-4 dependent. Thus IL-4 acted as a p olyclonal a cell activator in vivo and caused a cells to develop into IL-2 responsive cells. Furthermore, injection of IL-2 inhibited IgG1 a nd IgE production by Nb-inoculated mice. To understand the mechanism o f this IL-2-mediated inhibition, we used an in vitro IgG1 and IgE indu ction system. B cells from Nb-inoculated mice displayed an increase in the capacity of IL-2 to inhibit lipopolysaccharide (LPS) plus IL-4-dr iven IgE and IgG1 production, indicating that B cells expressing IL-PR P are highly sensitive to IL-2. This inhibition was principally depend ent upon the direct action of IL-2 on a cells. However, partial abolit ion of IL-2 inhibitory action by anti-IFN-gamma treatment suggested th at endogenous IFN-gamma released from IL-2-stimulated cells was also i nvolved in this IL-2-mediated IgE and IgG1 inhibition. Northern blot a nalysis demonstrated that IL-2 inhibited IL-4 induction of germline an d productive C-epsilon transcripts in LPS-stimulated a cells. Digestio n-circularization polymerase chain reaction analysis revealed IL-2 inh ibited IL-4 induction of s mu-s gamma 1 rearrangement in LPS-stimulate d B cells.