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.

Dual Role of Interleukin-1α in Delayed-Type Hypersensitivity and Airway Hyperresponsiveness

“…Both Th1 and Th2 immunity were observed after immunization with different adjuvants [15,16]. Sensitization with KLH (plus alum) induced strong Th2-mediated humoral responses [49,50]. Using this Th2-type model disease, we observed that IL-1 administration during sensitization abrogated disease and preferentially induced IFN-γ as compared to Th2-associated IL-5.…”

Basophils Are the Major Producers of IL-4 during Primary Helminth Infection

“…Even in the case of KLH/Alum, which led to a 16-fold increase of lung eosinophils lung basophils were not markedly increased. The comparison of a primary helminth infection with allergen challenge models is not exactly parallel since mice sensitized with KLH/alum and OVA/alum both had specific IgE present (31) and loaded on their basophils at the time of intranasal allergen challenge whereas no specific IgE was present at the time of primary helminth infection. Thus we evaluated blood basophilia during KLH/alum and OVA/alum sensitization and determined that initial priming with KLH/alum and OVA/alum led to an increase in the level of circulating basophils (Fig S1A), whilst the CD4+GFP+ cell levels remained unchanged (Fig S1B).…”

Local production and detection of (specific) IgE in nasal B-cells and plasma cells of allergic rhinitis patients

“…It is not possible to differentiate between IgE-positive B-cells if they are IgE-positive memory B-cells or at least activated B-cells [27]. Once formed, the switched IgE-positive memory B-cells are long-lived cells, but not all IgE responses lead to the formation of IgE-positive memory B-cells [28]. The present data suggest that the maturation of IgE-expressing Bcells (activated or memory) to IgE-producing plasma cells takes places in the nose.…”