title: The development of IgE+ memory B cells following primary IgE immune responses.
abstract: 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.
authors.affiliation: Department of Asthma/Allergy, Pharma Research, Ciba, Basel, Switzerland. mimrglg@wnmeds.ac.nz
authors.forename: G
authors.initials: G
authors.lastname: Le Gros
authors.forename: N
authors.initials: N
authors.lastname: Schultze
authors.forename: S
authors.initials: S
authors.lastname: Walti
authors.forename: K
authors.initials: K
authors.lastname: Einsle
authors.forename: F
authors.initials: F
authors.lastname: Finkelman
authors.forename: M H
authors.initials: MH
authors.lastname: Kosco-Vilbois
authors.forename: C
authors.initials: C
authors.lastname: Heusser
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000378:metabolism*; D007114:Immunization; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D009559:Nippostrongylus / Q000276:immunology
chemical_list: D000909:Antibodies, Helminth; D007073:Immunoglobulin E