IL-4 has been shown to induce B lymphocytes to switch from the expression of membrane
IgM to the expression of membrane
IgE and to be required for the generation of primary polyclonal and secondary Ag-specific
IgE responses in mice. To further define the role of
IL-4 in the generation of memory
IgE responses, we investigated the ability of a combination of anti-IL-4 and anti-IL-4R mAb to block the generation of secondary
IgE responses induced by: 1) a second
infection with the nematode parasites Nippostrongylus brasiliensis or Heligmosomoides polygyrus; or 2) injection of
anti-IgD antibody-primed mice with
anti-IgE antibody. The latter stimulus was designed to induce intrinsic membrane
IgE-expressing B cells to differentiate into
IgE-secreting cells. Although the
IgE responses induced by a second
nematode infection were completely inhibited by the combination of anti-IL-4 and anti-IL-4R mAb,
anti-IgE antibody-induced
IgE responses in
anti-IgD primed mice were not inhibited by these
antibodies to a large degree. Additional experiments demonstrated that the
anti-IgE antibody-induced memory
IgE response was dependent on CD4+ T cells but did not involve the low affinity B cell
Fc epsilon RII. Taken together, these observations provide evidence that IL-4 is required for virgin B lymphocytes to develop into
IgE-expressing cells, but is not required for B cells that express intrinsic membrane
IgE to differentiate into
IgE-secreting cells in a T-dependent response. Furthermore, these data suggest that secondary
IgE responses in the parasite models that we have studied develop from B cells that had not previously switched to the expression of
IgE.