title: Features of the overexpressed V1-69 genes in the unmutated subset of chronic lymphocytic leukemia are distinct from those in the healthy elderly repertoire.
abstract: Chronic lymphocytic leukemia (CLL) comprises 2 subsets, distinguished by expression of unmutated or mutated V(H) genes, with the former having a worse prognosis. Biased usage of the V1-69 gene is found in unmutated cases and is combined with selected D gene segments and J(H)6. It is controversial whether this is a CLL-associated feature or mirrors the normal B-cell pattern. Since CLL is a disease of the elderly, where changes in the B-cell repertoire may occur, we have analyzed V1-69 usage in the elderly (older than 75 years) population. Using monoclonal antibody (MoAb) G6, specific for 51p1-related V1-69 alleles, we found no increased expression with age. In 51p1-encoded immunoglobulin M (IgM), complementarity-determining region 3 (CDR3) length and frequency of D and J(H) genes were similar to those in the healthy young and distinct from those in CLL. These findings support the concept that CLL arises from B cells driven by antigen/superantigen and is not a stochastic event in the elderly B-cell population.
authors.affiliation: Molecular Immunology Group, Tenovus Laboratory, Southampton University Hospitals Trust, Southampton, United Kingdom. kp1@soton.ac.uk
authors.forename: Kathleen N
authors.initials: KN
authors.lastname: Potter
authors.forename: Jenny
authors.initials: J
authors.lastname: Orchard
authors.forename: Eustacia
authors.initials: E
authors.lastname: Critchley
authors.forename: C Ian
authors.initials: CI
authors.lastname: Mockridge
authors.forename: Annette
authors.initials: A
authors.lastname: Jose
authors.forename: Freda K
authors.initials: FK
authors.lastname: Stevenson
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000737:chemistry / Q000473:pathology; D018956:CD5 Antigens / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D015723:Gene Library; D015322:Gene Rearrangement, B-Lymphocyte; D005803:Genes, Immunoglobulin; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000473:pathology; D018089:Superantigens / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D018956:CD5 Antigens; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D009363:Neoplasm Proteins; D018089:Superantigens