The development of IgE(+) memory B cells following primary IgE immune responses

We studied whether long-lived IgE(+) memory B cells develop following three types of primary IgE immune responses. Immunization of mice with anti-IgD antibody induced a T cell-dependent, interleukin (IL)-4-dependent primary IgE response and the formation of IgE isotype switched (IgE(+)) memory B cells. These IgE(+) memory B cells could be stimulated in vivo by injection with goat anti-IgE antibodies to produce a profound IL-4-independent memory IgE response. By contrast, both infection of mice with Nippostrongylus brasiliensis or repeated immunization with benzylpenicilloyl-keyhole limpet hemocyanin (BPO-KLH) in alum stimulated good primary IgE responses and profound memory T cell-dependent antigen-specific IgE responses, but failed to induce the development of long lived IgE(+) memory B cells because they could not be recalled with goat anti-IgE antibodies. Mice receiving double immunizations combining anti-IgD with either N. brasiliensis infection or BPO-KLH immunization mounted significant goat anti-IgE-induced secondary IgE responses, but no N. brasiliensis or BPO-KLH-specific IgE could be detected. This indicates that the N. brasiliensis and BPO-KLH induced immune responses do not suppress the development of IgE(+) B cells, but rather, do not provide the necessary conditions for their formation. Taken together these data indicate that long-lived IgE(+) B cells fail to develop during the primary IgE response to N. brasiliensis infection or BPO-KLH immunization. By contrast, significant numbers of IgE(+) memory B cells form during the primary IgE immune response induced by anti-IgD immunization. Our observations suggest that immunization protocols involving membrane IgD cross-linking and limited duration of cognate T cell help are necessary for the formation of IgE(+) memory B cells. It will be important to determine the relevance of membrane IgD interaction with allergens, as this would influence the design of new therapies for the treatment of allergy and asthma.