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

Abstract

Van Ommen R, Vredendaal AECM, Savelkoul HFJ. Secondary IgE Responses In Vivo are Predominantly Generated Via 7i€-Double Positive B Cells. Scand J Immunol 1993;40:491-50I We have recently developed a model in which mice were treated with IL-4 after primary immunization, resulting in elevated tolal serum IgGi 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 7iC-double positive B-cell population which is increased as a result of IL-4 treatment. Moreover, it is shown that 7ie-double positive B cells can develop in vitro out of 71-positive primed B cells and that these double positive cells can differentiate into IgGr and IgE-secreting cells. The existence of 7ie-double positive memory B cells can explain the differences in cytokine dependence of TNP-specific memory IgGj and IgE responses found after adoptively transferring primed spleen cells into irradiated naive recipients. Whereas the IL-4 independent TNP-specific memory IgGi 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-7, 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 lo IgG|, or are double positive for IgG| and IgE, thereby suggesting a minor role for e-single positive B cells in secondary IgE responses.

Stimulation of allergen-loaded macrophages by TLR9-ligand potentiates IL-10-mediated suppression of allergic airway inflammation in mice

“…The observation that the suppression of IgE is partially IL-10 independent suggests that the suppression of serum IgE levels is only slightly correlated to Th2-cytokine levels. This is in agreement with the finding that memory IgE responses are inferior mediated by Th2 cytokines [39]. These data indicate that a second, IL-10 independent, suppressive pathway has to be induced by OVA-Mφ that causes a further suppression of serum IgE levels.…”

The Role of Interleukin‐4 in the Regulation of Sequential Isotype Switch from Immunoglobulin G1 to Immunoglobulin E Antibody Production

“…As a result of activation by primed CD4 T cells IgG1-positive B cells expand, and up to a certain ratio develop after a sequential isotype switch into IgE AFC [15, 21, 34±36]. The process of sequential isotype switch would explain the simultaneous expression of intracellular or surface IgG1 and IgE on B cells observed by others [15,37,38]. Consequently, the limited capacity of B cells from K01 mice to generate IgE AFC after cultivation is because of the low number of IgG1-expressing intermediates, whereas the augmented expression of IgG1 antibody in mice primed with high doses of KLH is the prerequisite for the increased appearance of IgE AFC in K100 cultures.…”

Receptor-Mediated and Lectin-Like Activities of Carp (Cyprinus carpio) TNF-α

“…At various time points after stimulation, cells were collected and washed once in cold cRPMI medium. To remove any receptor-bound soluble TNF-␣, cells were first acid-treated as described previously (74) and subsequently analyzed by flow cytometry. Surface-bound TNF-␣ was detected using affinity-purified rabbit-anti-carp TNF-␣ IgG.…”