Immunoglobulin gene rearrangement, repertoire diversity, and the allergic response.
The immunoglobulin repertoire arises as a consequence of combinatorial diversity, junctional diversity, and the process of somatic point mutation. Each of these processes involves biases that limit and shape the available immunoglobulin repertoire. The expressed repertoire is further shaped by selection, to the extent that biased gene usage can become apparent in many disease states. The study of rearranged immunoglobulin genes therefore may not only provide insights into the molecular processes involved in the generation of antibody diversity but also inform us of pathogenic processes and perhaps identify particular lymphocyte clones as therapeutic targets. Partly as a consequence of the low numbers of circulating IgE-committed B-cells, studies of rearranged IgE genes in allergic individuals have commenced relatively recently. In this review, recent advances in our understanding of the processes of immunoglobulin gene rearrangement and somatic point mutation are described, and biases inherent to these processes are discussed. The evidence that some diseases may be associated with particular gene rearrangements is then considered, with a particular focus on allergic disease. Reviewed data suggest that an important contribution to the IgE response may come from cells that use relatively rare heavy chain V (V(H)) segment genes, which display little somatic point mutation. Some IgE antibodies also seem to display polyreactive binding. In other contexts, these 3 characteristics have been associated with antibodies of the B-1 B-cell subset, and the possibility that B-1 B-cells contribute to the allergic response is therefore considered.
Collins
A M
AM
School of Biotechnology and Biomolecular Sciences, University of New South Wales, New South Wales, Sydney, Australia. a.collins@unsw.edu.au
Sewell
W A
WA
Edwards
M R
MR
D000916:Antibody Diversity; D001402:B-Lymphocytes / Q000276:immunology; D005785:Gene Conversion; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000235:genetics / Q000276:immunology; D017354:Point Mutation
D007073:Immunoglobulin E