Research described in this proposal will enhance our capacity to classify and treat human B cell malignancies. Molecular tools will be generated that permit the rapid isolation and/or identification of the immunoglobulin (Ig) variable region genes (V genes) expressed by clonal populations of malignant B cells. With such tools we may examine the molecular basis for the high frequency expression of particular Ig V genes in CD5 B cell malignancies. In addition, we will immunize mice with either human Igs potentially possessing conserved cross-reactive idiotypes (CRIs), or synthetic peptides, that mimic conserved Ig variable region framework epitopes, to generate anti-idiotype or anti-framework antibody-producing hybridomas that will be selected using the fluorescence activated cell sorter. In total, these tools may allow us to distinguish B cell malignancies with respect to Ig V gene utilization. They also will allow us to examine Ig gene expression by CD5 B cells isolated from normal volunteers and unaffected siblings of patients with CD5 B cell malignancies. Through these studies we may gain insight into physiology of Ig V gene expression and factors contributing to B cell neoplasia. Finally, these reagents will allow us rapidly to characterize clonally distributed antibody variable region determinants that may be targeted for active immunotherapy in a pilot phase I study testing the safety of synthetic peptide vaccines.
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