Secondary IgE Responses In Vivo are Predominantly Generated Via γ1ɛ‐Double Positive B Cells

We have recently developed a model in which mice were treated with 1L‐4 after primary immunization, resulting in elevated total serum IgG 1 and IgE levels, but decreased antigen‐specific levels and memory formation for these isotypes. In this report, we describe that these effects of IL‐4 are mediated at the B cell and not the T‐cell level. Major changes occurred in the γ1ɛ‐double positive B‐cell population which is increased as a result of IL‐4 treatment. Moreover, it is shown that γ1ɛ‐double positive B cells can develop in vitro out of γ1‐positive primed B cells and that these double positive cells can differentiate into IgG 1 ‐ and IgE‐secreting cells. The existence of γ1ɛ‐double positive memory B cells can explain the differences in cytokine dependence of TNP‐specific memory IgG 1 and IgE responses found after adoptively transferring primed spleen cells into irradiated naive recipients. Whereas the IL‐4 independent TNP‐specific memory IgG 1 responses could be blocked efficiently by neutralizing IL‐5 and IL‐6, TNP‐specific memory IgE responses were virtually not susceptible to such treatment. These IgE responses were also not susceptible to IFN‐γ, used in doses that could inhibit the primary IgE response. Inhibition of the TNP‐specific memory IgG 1 response by neutralizing IL‐5 and IL‐6 is accompanied by a 10‐fold increase of the IL‐4 independent TNP‐specific IgE memory response. These data indicate that secondary IgE responses primarily result from B cells that are either switched to IgG 1 , or are double positive for IgG 1 and IgE, thereby suggesting a minor role for ɛ‐single positive B cells in secondary IgE responses.