Allergen Drives Class Switching to IgE in the Nasal Mucosa in Allergic Rhinitis

Abstract

IgE-expressing B cells are over 1000 times more frequent in the nasal B cell than the peripheral blood B cell population. We have investigated the provenance of these B cells in the nasal mucosa in allergic rhinitis. It is generally accepted that expression of activation-induced cytidine deaminase and class switch recombination (CSR) occur in lymphoid tissue, implying that IgE-committed B cells must migrate through the circulation to the nasal mucosa. Our detection of mRNA for activation-induced cytidine, multiple germline gene transcripts, and ε circle transcripts in the nasal mucosa of allergic, in contrast to nonallergic control subjects, however, indicates that local CSR occurs in allergic rhinitis. The germline gene transcripts and ε circle transcripts in grass pollen-allergic subjects are up-regulated during the season and also when biopsies from allergic subjects are incubated with the allergen ex vivo. These results demonstrate that allergen stimulates local CSR to IgE, revealing a potential target for topical therapies in allergic rhinitis.

Isoallergen Variations Contribute to the Overall Complexity of Effector Cell Degranulation: Effect Mediated through Differentiated IgE Affinity

“…In the fairly limited number of papers (19)(20)(21)(22)(23), including this one, in which human allergenspecific IgE Ab fragments have been isolated, combinatorial libraries have always been cloned from peripheral blood samples. However, an essential aspect of the evolving IgE response is the accumulating evidence that both class-switch recombination (24)(25)(26)(27) and somatic hypermutation (25) followed by clonal expansion and IgE production (28,29) occur in local airway mucosa under the influence of the inflamed tissue (reviewed in Ref. 30).…”

Fecal antibody levels as a noninvasive method for measuring immunity to gastrointestinal nematodes in ecological studies

“…1986; Takhar et al. 2005). With respect to function of these isotypes, there are some notable differences: IgA, unlike IgG, is poor at activating complement and acting as an opsonin and is largely thought to act by binding to and neutralizing invading pathogens (Brandtzaeg 2013; Gutzeit et al.…”

Important research questions in allergy and related diseases: nonallergic rhinitis: a GA2LEN paper

“…Local IgE response should be studied by nasal challenge with allergens (12). Local IgE production should be tested and compared in allergic and NAR (70)(71)(72).…”