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.
Le Gros
G
G
Department of Asthma/Allergy, Pharma Research, Ciba, Basel, Switzerland. mimrglg@wnmeds.ac.nz
Schultze
N
N
Walti
S
S
Einsle
K
K
Finkelman
F
F
Kosco-Vilbois
M H
MH
Heusser
C
C
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
D000909:Antibodies, Helminth; D007073:Immunoglobulin E