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 VH 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 VH 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 VH5 to locate amino acids of interest.


RESULTS
We observed a significantly increased frequency of IgE and IgA VH5 transcripts in the nasal mucosa of the allergic patients compared with the normal PBMC repertoire. Within IgE and IgA VH5 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 VH5 sequences were in framework region 1. The hotspots and a conserved VH5-specific framework residue form a tight cluster on the surface of VH5.


CONCLUSIONS
Our results provide evidence for the activity of a superantigen in the nasal mucosa in patients with allergic rhinitis.
Coker
Heather A
HA
The Randall Division of Cell and Molecular Biophysics, King's College London, London.
Harries
Helen E
HE
Banfield
Graham K
GK
Carr
Victoria A
VA
Durham
Stephen R
SR
Chevretton
Elfy
E
Hobby
Paul
P
Sutton
Brian J
BJ
Gould
Hannah J
HJ
D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics; D007073:Immunoglobulin E / Q000737:chemistry / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009297:Nasal Mucosa / Q000276:immunology*; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology*
D007070:Immunoglobulin A; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007073:Immunoglobulin E