title: Immunoglobulin heavy- and light-chain repertoire in splenic marginal zone lymphoma.
abstract: The considerable heterogeneity in morphology, immunophenotype, genotype, and clinical behavior of splenic marginal zone lymphoma (SMZL) hinders firm conclusions on the origin and differentiation stage of the neoplastic cells. Immunoglobulin (IG) gene usage and somatic mutation patterns were studied in a series of 43 SMZL cases. Clonal IGHV-D-J rearrangements were amplified in 42/43 cases (4 cases carried double rearrangements). Among IGHV-D-J rearrangements, IGHV3 and IGHV4 subgroup genes were used with the highest frequency. Nineteen IGHV genes were unmutated (> 98% homology to the closest germline IGHV gene), whereas 27/46 were mutated. Clonal IGKV-J and IGLV-J gene rearrangements were amplified in 36/43 cases, including 31 IGKV-J (8/31 in lambda light-chain expressing cases) and 12 IGLV-J rearrangements; 9/31 IGKV and 6/12 IGLV sequences were mutated. IGKV-J and IGLV-J rearrangements used 14 IGKV and 9 IGLV different germline genes. Significant evidence for positive selection by classical T-dependent antigen was found in only 5/27 IGHV and 6/15 IGKV+IGLV mutated genes. These results provide evidence for the diverse B-cell subpopulations residing in the SMZ, which could represent physiologic equivalents of distinct SMZL subtypes. Furthermore, they indicate that in SMZL, as in other B cell malignancies, a complementarity imprint of antigen selection might be witnessed either by IGHV, IGKV, or IGLV rearranged sequences.
authors.affiliation: Hematology Department, G. Papanicolaou Hospital, Thessaloniki. Greece. stavstam@otenet.gr
authors.forename: Kostas
authors.initials: K
authors.lastname: Stamatopoulos
authors.forename: Chrysoula
authors.initials: C
authors.lastname: Belessi
authors.forename: Theodora
authors.initials: T
authors.lastname: Papadaki
authors.forename: Evangelia
authors.initials: E
authors.lastname: Kalagiakou
authors.forename: Niki
authors.initials: N
authors.lastname: Stavroyianni
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Douka
authors.forename: Stavroula
authors.initials: S
authors.lastname: Afendaki
authors.forename: Riad
authors.initials: R
authors.lastname: Saloum
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Parasi
authors.forename: Dimitra
authors.initials: D
authors.lastname: Anagnostou
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Laoutaris
authors.forename: Athanasios
authors.initials: A
authors.lastname: Fassas
authors.forename: Achilles
authors.initials: A
authors.lastname: Anagnostopoulos
mesh_terms: D022801:Complementarity Determining Regions / Q000235:genetics; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics*; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain / Q000235:genetics*; D006801:Humans; D007125:Immunogenetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D008223:Lymphoma / Q000235:genetics* / Q000276:immunology; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*; D013160:Splenic Neoplasms / Q000235:genetics* / Q000276:immunology
chemical_list: D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007145:Immunoglobulin kappa-Chains