The Effects of Somatic Mutation on the Binding Avidities of Antibodies in the HUG transgene Model.

Abstract

Immunoglobulin (Ig) diversity stems from the rearrangement of Ig genes (VDJ rearrangement) during B lymphocyte development. Further diversity and Ig specificity is determined by somatic mutation in the rearranged variable regions of the Ig genes after contact with the antigen. Interaction with the antigen coupled with signals from T lymphocytes induces random point mutations in the rearranged variable regions of B-lymphocytes. Mutations that result in higher antibody affinity for the antigen trigger selective proliferation of the cells containing those mutations. HUG transgenic mice were immunized with the antigen (dansyl) recognized by the transgene in order to induce somatic mutation of the transgene. The HUG antibodies can be assayed for using Enzyme Linked Immunosorbent Assays (ELISAs). We also use ELISAs to screen for avidity changes in the mutated Igs. My experiment includes avidity testing of mutated Igs using ELISA. The goal is to determine whether or not a transgenic immunoglobulin can undergo somatic mutation and affinity maturation.