THE DEVELOPMENT OF IGE(-CELLS FOLLOWING PRIMARY IGE IMMUNE-RESPONSES() MEMORY B)

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-depe ndent primary IgE response and the formation of IgE isotype switched ( IgE(+)) memory B cells. These IgE(+) memory B cells could be stimulate d in vivo by injection with goat anti-IgE antibodies to produce a prof ound IL-4-independent memory IgE response. By contrast, both infection of mice with Nippostrongylus brasiliensis or repeated immunization wi th benzylpenicilloyl-keyhole limpet hemocyanin (BPO-KLH) in alum stimu lated good primary IgE responses and profound memory T cell-dependent antigen-specific IgE responses, but failed to induce the development o f long lived IgE(+) memory B cells because they could not be recalled with goat anti-IgE antibodies. Mice receiving double immunizations com bining anti-IgD with either N. brasiliensis infection or BPO-KLH immun ization mounted significant goat anti-IgE-induced secondary IgE respon ses, but no N. brasiliensis or BPO-KLH-specific IgE could be detected. This indicates that the N. brasiliensis and BPO-KLH induced immune re sponses do not suppress the development of IgE(+) B cells, but rather, do not provide the necessary conditions for their formation. Taken to gether these data indicate that long-lived IgE(+) B cells fail to deve lop during the primary IgE response to N. brasiliensis infection or BP O-KLH immunization. By contrast, significant numbers of IgE(+) memory B cells form during the primary IgE immune response induced by anti-Ig D immunization. Our observations suggest that immunization protocols i nvolving 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 interact ion with allergens, as this would influence the design of new therapie s for the treatment of allergy and asthma.