VH gene usage in immunoglobulin E responses of seasonal rhinitis patients allergic to grass pollen is oligoclonal and antigen driven

Davies, J. M. and O'Hehir, R. E. (2004) VH gene usage in immunoglobulin E responses of seasonal rhinitis patients allergic to grass pollen is oligoclonal and antigen driven. Clinical and Experimental Allergy, 34 3: 429-436. doi:10.1111/j.1365-2222.2004.01900.x


Author Davies, J. M.
O'Hehir, R. E.
Title VH gene usage in immunoglobulin E responses of seasonal rhinitis patients allergic to grass pollen is oligoclonal and antigen driven
Journal name Clinical and Experimental Allergy   Check publisher's open access policy
ISSN 1365-2222
0954-7894
Publication date 2004-01-01
Sub-type Article (original research)
DOI 10.1111/j.1365-2222.2004.01900.x
Open Access Status
Volume 34
Issue 3
Start page 429
End page 436
Total pages 8
Place of publication Oxford, England
Publisher Blackwell Science
Language eng
Subject 11 Medical and Health Sciences
1107 Immunology
Formatted abstract
Background
IgE is the pivotal-specific effector molecule of allergic reactions yet it remains unclear whether the elevated production of IgE in atopic individuals is due to superantigen activation of B cell populations, increased antibody class switching to IgE or oligoclonal allergen-driven IgE responses.

Objectives

To increase our understanding of the mechanisms driving IgE responses in allergic disease we examined immunoglobulin variable regions of IgE heavy chain transcripts from three patients with seasonal rhinitis due to grass pollen allergy.

Methods
Variable domain of heavy chain-epsilon constant domain 1 cDNAs were amplified from peripheral blood using a two-step semi-nested PCR, cloned and sequenced.

Results

The VH gene family usage in subject A was broadly based, but there were two clusters of sequences using genes VH 3-9 and 3-11 with unusually low levels of somatic mutations, 0–3%. Subject B repeatedly used VH 1-69 and subject C repeatedly used VH 1-02, 1-46 and 5a genes. Most clones were highly mutated being only 86–95% homologous to their germline VH gene counterparts and somatic mutations were more abundant at the complementarity determining rather than framework regions. Multiple sequence alignment revealed both repeated use of particular VH genes as well as clonal relatedness among clusters of IgE transcripts.

Conclusion
In contrast to previous studies we observed no preferred VH gene common to IgE transcripts of the three subjects allergic to grass pollen. Moreover, most of the VH gene characteristics of the IgE transcripts were consistent with oligoclonal antigen-driven IgE responses.
Keyword Complementarity determining region
IgE
Seasonal rhinitis
Somatic hypermutation
VH gene
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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Created: Wed, 15 Apr 2009, 21:12:48 EST by Ms Sarada Rao on behalf of Faculty Of Health Sciences