Secondary IgE responses in vivo are predominantly generated via gamma 1 epsilon-double positive B cells.
We have recently developed a model in which mice were treated with IL-4 after primary immunization, resulting in elevated total serum IgG1 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 gamma 1 epsilon-double positive B-cell population which is increased as a result of IL-4 treatment. Moreover, it is shown that gamma 1 epsilon-double positive B cells can develop in vitro out of gamma 1-positive primed B cells and that these double positive cells can differentiate into IgG1- and IgE-secreting cells. The existence of gamma 1 epsilon-double positive memory B cells can explain the differences in cytokine dependence of TNP-specific memory IgG1 and IgE responses found after adoptively transferring primed spleen cells into irradiated naive recipients. Whereas the IL-4 independent TNP-specific memory IgG1 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-gamma, used in doses that could inhibit the primary IgE response. Inhibition of the TNP-specific memory IgG1 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 IgG1, or are double positive for IgG1 and IgE, thereby suggesting a minor role for epsilon-single positive B cells in secondary IgE responses.
Department of Immunology, Erasmus University, Rotterdam, The Netherlands.
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R
Van Ommen
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AE
Vredendaal
H F
HF
Savelkoul
D000818:Animals; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005434:Flow Cytometry; D006241:Haptens; D006433:Hemocyanins / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007156:Immunologic Memory / Q000276:immunology; D016219:Immunotherapy, Adoptive; D015847:Interleukin-4 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology
D000941:Antigens; D006241:Haptens; D007074:Immunoglobulin G; C054401:trinitrophenyl keyhole limpet hemocyanin; D015847:Interleukin-4; D007073:Immunoglobulin E; D006433:Hemocyanins