Identification and characterization of a novel antigen from the nematode Nippostrongylus brasiliensis recognized by specific IgE.

Identification and characterization of IgE-inducing antigens are important for elucidating the mechanisms involved in IgE-mediated immune responses in allergic diseases and parasite infections. While many allergens have been characterized, little is known about parasite antigens inducing specific IgE following infection. In order to identify antigens from the nematode Nippostrongylus brasiliensis, we generated an IgE-producing B cell hybridoma from N. brasiliensis-infected C57BL/6 mice and constructed a cDNA phage display library from N. brasiliensis. We successfully cloned and expressed an N. brasiliensis antigen (Nb-Ag1) that showed specific binding to anti-N. brasiliensis IgE. Nb-Ag1 localized to the pharynx of adult N. brasiliensis, suggesting that Nb-Ag1 is a potential pharyngeal gland antigen. Nb-Ag1-specific IgE could be detected in the serum of N. brasiliensis-infected mice, but only for a short time and only following a challenge infection. In contrast, local administration of Nb-Ag1 during primary, secondary and tertiary infections induced Nb-Ag1-specific IgE-mediated active cutaneous anaphylaxis. Therefore, amongst the high amounts of polyclonal total IgE, low levels of parasite-specific IgE responses are induced during primary helminth infections. Here, we show that even such low levels of parasite-specific IgE are sufficient to prime mast cells in vivo and mediate degranulation.

Induction of IgE and allergic-type responses in fur mite-infested mice.

High serum IgE levels are characteristic of allergic diseases and immune responses to nematode parasites. A murine allergy model based on infestation with the fur mites Myocoptes musculinus and Myobia musculi was investigated. Analysis of mite infestation in various knockout mice revealed that IgE production in response to these ectoparasites was dependent on T cells, IL-4, and CD40L. Secretion of IL-4 by CD4+ T cells obtained from peripheral LN draining mite-infested skin sites was increased with progressing mite infestation and correlated with the serum IgE induction. A time course analysis of the mRNA expression of switched IgE, activation-induced cytidine deaminase (AID), and epsilon germ-line transcripts (epsilonGLT) suggested that switching to IgE in response to fur mites occurred initially in skin-draining LN. In addition, mite infestation induced mast cell degranulation in the skin as well as mast cell infiltration into skin-draining LN. Analysis of the immune response generated in mite-infested mice is a valuable model for the investigation of allergic disorders and provides information for better understanding of mechanisms involved in IgE induction and regulation in a physiological way of allergen-exposure resembling atopic sensitization in humans.

Natural IgE production in the absence of MHC Class II cognate help.

IgE induction by parasites and allergens is antigen driven and cognate T cell help dependent. We demonstrate that spontaneously produced IgE in T cell-deficient and germ-free wild-type (wt) mice is composed of natural specificities and induced by a mechanism independent of MHC class II (MHC II) cognate help. This does not require secondary lymphoid structures or germinal center formation, although some bystander T cell-derived IL-4 is necessary. The pathway of spontaneous IgE production is not inhibited by regulatory T cells and increases with age to constitute significant serum concentrations, even in naive animals.