title: Antigen receptors and somatic hypermutation in B-cell chronic lymphocytic leukemia with Richter's transformation.
abstract: OBJECTIVE
  Activation-induced cytidine deaminase is essential for somatic hypermutation and class switch recombination of the immunoglobulin genes in B cells. It has been proposed that aberrant targeting of the somatic hypermutation machinery is instrumental in initiation and progression of B-cell non Hodgkin's lymphomas. In this study, we investigated the B-cell receptor and the role of the somatic hypermutation machinery in B-cell chronic lymphocytic leukemias (B-CLL) prior to and after transformation to a lymphoma of a higher malignancy grade (Richter's transformation).
  
  
  METHODS
  We investigated the activity of the somatic hypermutation machinery in nine B-CLL and secondary diffuse large B-cell lymphomas by measuring the expression of activation-induced cytidine deaminase, in combination with mutation analysis of immunoglobulin (Ig) and non-Ig genes. Furthermore, the structure of the antigen receptors of B-CLL known to have developed a Richter's syndrome (RS B-CLL) was analyzed by comparing the most variable region of the Ig, the CDR3 region, to CDR3 sequences present in GenBank.
  
  
  RESULTS
  Ig variable heavy chain (IgV(H)) gene studies revealed that Richter's transformation occurs almost exclusively in unmutated B-CLL. Furthermore, activated-induced cytidine deaminase expression and somatic hypermutation activity of most RS B-CLL were found to be higher than those of control (non-transforming) B-CLL. Finally, comparison of the IgVH-CDR3 regions showed a remarkable amino acid sequence homology between two RS B-CLL of our panel and two RS B-CLL described in the literature.
  
  
  CONCLUSIONS
  The combined findings suggest a role for the Ig gene diversification apparatus during Richter's transformation and show that distinct RS-B-CLL may recognize recurrent antigenic epitopes.
authors.affiliation: Department of Pathology, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Smit
authors.forename: Febe
authors.initials: F
authors.lastname: van Maldegem
authors.forename: Anton W
authors.initials: AW
authors.lastname: Langerak
authors.forename: C Ellen
authors.initials: CE
authors.lastname: van der Schoot
authors.forename: Mireille J
authors.initials: MJ
authors.lastname: de Wit
authors.forename: Silvia
authors.initials: S
authors.lastname: Bea
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Bende
authors.forename: Carel J M
authors.initials: CJ
authors.lastname: van Noesel
mesh_terms: D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000473:pathology; D016609:Neoplasms, Second Primary; D011379:Prognosis; D011946:Receptors, Antigen / Q000276:immunology*; D027041:Somatic Hypermutation, Immunoglobulin
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D011946:Receptors, Antigen