VH gene usage in IgE in patients with atopic asthma

Snow, Rachel Elizabeth (1998) VH gene usage in IgE in patients with atopic asthma. University of Southampton, Doctoral Thesis.

Abstract

The spectrum of V_H-D-J_H sequences of IgE antibodies from atopic asthmatic patients has been studied.

An initial investigation of these sequences from the spleen of an asthmatic patient revealed preferential usage of the V_H5 family, with 5 out of 14 clones being derived from this family. A control PCR of the same V_H primers in combination with J_H yielded only 1 out of 13 sequences from the V_H5 family indicating preferential usage of V_H5 only for IgE. Clones were also obtained from the larger families, V_H3 and V_H4. All the sequences showed extensive somatic hypermutation, with some of the V_H3 and V_H4-derived clones demonstrating evidence of conventional antigen selection.

Using the same approach with peripheral blood from 7 patients, the minor V_H5 family was represented in 17% of V_H-C_ε transcripts. By contrast, control PCRs with IgM primers replacing those for IgE obtained a 5% incidence of the V_H5 family. These findings have led to the suggestion that common allergens may be acting as B cell superantigens and driving the selection of the V_H5 genes.

The results point to three processes that influence the generation of IgE antibodies.

1) Preferential usage of the V_H5 genes, indicative of stimulation by a superantigen.

2) Extensive somatic hypermutation, with hotspots common to V_H5 genes.

3) Conventional antigen selection of higher affinity mutants and B cells expressing other V_H genes.

Serum levels of antigen specific IgG4 are often raised along with IgE in allergic individuals. These IgG4 antibodies may have a protective role as 'blocking antibodies', reducing the harmful effects of IgE by competing for antigen. The clonal relationship of IgG4 and IgE in allergic patients has been investigated by PCR. In ¾ patients V_H5-Cγ4 transcripts were identified clonally related to IgE. These findings suggest that an IgM precursor cell may commonly switch to both IgG4 and IgE.

This record has no associated files available for download.

Contributors

Download statistics