Biased use of VH5 IgE-positive B cells in the nasal mucosa in allergic rhinitis

Background: IgE antibody-producing B cells are enriched in the nasal mucosa in patients with allergic rhinitis because of local class switching to IgE. The expressed IgE V-H genes also undergo somatic hypermutation in situ to generate clonal families. The antigenic driving force behind these events is unknown. Objective: To examine the possible involvement of a superantigen in allergic rhinitis, we compared the variable (VH) gene use and patterns of somatic mutation in the expressed IgE heavy-chain genes in nasal biopsy specimens and blood from allergic patients and the IgA Vu use in the same biopsy specimens and also those from nonallergic controls. Methods: We extracted mRNA from the nasal biopsy specimens of 13 patients and 4 nonallergic control subjects and PBMCs from 7 allergic patients. IgE and IgA VH regions were RT-PCR amplified, and the DNA sequences were compared with those of control subjects. We constructed a molecular model of V(H)5 to locate amino acids of interest. Results: We observed a significantly increased frequency of IgE and IgA V(H)5 transcripts in the nasal mucosa of the allergic patients compared with the normal PBMC repertoire. Within IgE and IgA V(H)5 sequences in the nasal mucosa, the distribution of replacement amino acids was skewed toward the immunoglobulin framework regions. Three of 4 nonintrinsic hotspots of mutation identified in the V(H)5 sequences were in framework region 1. The hotspots and a conserved V(H)5-specific framework residue form a tight cluster on the surface of V(H)5. Conclusion: Our results provide evidence for the activity of a superantigen in the nasal mucosa in patients with allergic rhinitis.