title: Somatic hypermutation and V(H) gene usage in mantle cell lymphoma.
abstract: Mantle cell lymphoma (MCL) is considered to derive from naïve, pregerminal center (GC) CD5+ B-cells. However, the cell of origin has been questioned in recent studies that showed somatic hypermutations in the immunoglobulin (Ig) variable heavy chain (V(H)) genes in subsets of MCL. To clarify this issue, we analyzed the IgV(H) genes for the presence of somatic hypermutations in 51 MCL cases. Twenty percent of the MCL cases displayed somatically mutated V(H) genes (defined as >2% mutated), whereas 80% showed unmutated V(H) genes. This finding suggests that MCL is a genetically heterogeneous disease, with the majority of cases originating from unmutated pre-GC B-cells and a subset deriving from more mature B-cells which have been exposed to the GC environment and have undergone somatic hypermutation. A biased V(H) gene usage has been demonstrated in several B-cell malignancies; however, this has not yet been investigated in MCL, although V(H)4-34 overusage has been indicated by small studies. Interestingly, we found a restricted usage of three individual V(H) genes in our MCL material; V(H)4-34 (22%), V(H)3-21 (16%) and V(H)5-51 (12%). This novel finding of preferential V(H) gene usage in half of the MCL cases may suggest an antigen driven process occurring in B-cells expressing specific VH genes, thus implicating that Ig specificity could be involved in mantle cell lymphoma development.
authors.affiliation: Department of Genetics and Pathology, Uppsala University, Sweden.
authors.forename: Mia
authors.initials: M
authors.lastname: Thorsélius
authors.forename: Sarah
authors.initials: S
authors.lastname: Walsh
authors.forename: Inger
authors.initials: I
authors.lastname: Eriksson
authors.forename: Ulf
authors.initials: U
authors.lastname: Thunberg
authors.forename: Anna
authors.initials: A
authors.lastname: Johnson
authors.forename: Carin
authors.initials: C
authors.lastname: Backlin
authors.forename: Gunilla
authors.initials: G
authors.lastname: Enblad
authors.forename: Christer
authors.initials: C
authors.lastname: Sundström
authors.forename: Göran
authors.initials: G
authors.lastname: Roos
authors.forename: Richard
authors.initials: R
authors.lastname: Rosenquist
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D005260:Female; D005803:Genes, Immunoglobulin; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D020522:Lymphoma, Mantle-Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D027041:Somatic Hypermutation, Immunoglobulin
chemical_list: D007135:Immunoglobulin Variable Region