The present project was designed to gain insight into the possible influence of antigenic microenvironment selection on the neoplastic transformation of MBL, through the following specific objectives:
1) Extensive characterization of clonal cells from healthy subjects with CLL-like MBL, patients with B-CLL and their first-degree relatives, native of the same geographical area (Salamanca), by high-sensitive flow cytometry and detection of specific genetic alterations by fluorescence in situ hybridization (FISH).
2) Sensitive molecular dissections of B-cell antigen receptor (BCR) in the small aberrant B-cell clones, purified by flow cytometry, by analysis of the immunoglobulin variable region gene (IGV).
3) Identification of molecular characteristics of IGV sequences shared by the clonal B cells of the different individuals to predict recognition of common antigenic stimuli by using computational and data mining methods. Subsequent serological studies to test for the presence of specific antibodies against the antigen signatures obtained.