Sequence Analysis of Germline and Expressed Immunoglobin Genes

Felix Breden

Abstract

One of the responses of the body to infection is to produce antibodies to foreign antigens (mostly viruses and bacteria) have evolved to produce a very diverse antibody response to the huge diversity of pathogens to which we are exposed. The first step in the creation of antibody diversity is the recombination of various V, J, and D gene segments within the genome of a developing B cell to produce a functional antibody gene. The second step occurs when that B cell's antibody gene is further diversified by somatic mutation. In this manner, B cells producing the tightest-binding antibodies are selected by antigen, with the selection being based on both the gene segments that the B cell uses, and the somatic mutations that arise in that B cell clone.More and more sequences of expressed antibody genes are being examined in patients with specific diseases. Based on these sequences, researchers have observed distinct patterns of V-gene usage and somatic mutation. For example, specific types of somatic mutations are characteristic of autoimmune diseases, whereas HIV-1 infection may be characterized by the use of certain families of V-Genes.This more sophisticated and statistically sound understanding of the patterns of V-gene usage and somatic mutation is critical to both vaccine development and understanding autoimmune diseases.

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