title: Mantle cell lymphoma with t(11;14) and unmutated or mutated VH genes expresses AID and undergoes isotype switch events.
abstract: Isotype switch commonly follows onset of somatic hypermutation in the germinal center (GC), with activation-induced cytidine deaminase (AID) as a prerequisite. Mantle cell lymphoma (MCL) with t(11;14) includes a subset with unmutated (UM) and a minor subset with mutated (MUT) VH genes. Here, we investigated whether switch events and AID expression occur in MCL. In 4 of 6 UM and 4 of 7 MUT MCLs, alternative tumor-derived Cgamma,alpha,epsilon transcripts were identified. AID transcripts, including a splice variant, were common to both subsets. AID expression correlated with switch in 8 of 8 cases, but in 3 of 5 cases it occurred with switch absent. Circle transcripts (Igamma-Cmicro/Ialpha-Cmu) were identified in 5 of 7 evaluated cases. In 1 of 12 cases, 12% of tumor cells expressed immunoglobulin L-restricted surface IgA. Ongoing switch recombination events appear to be a feature of MCL, likely restricted to a minor tumor subpopulation, with occasional variant sIg expression. UM MCLs implicate origins from pre-GC B cells and reveal switch events at ectopic sites.
authors.affiliation: Molecular Immunology Group, Tenovus Laboratory, Southampton University Hospitals, UK.
authors.forename: Gavin
authors.initials: G
authors.lastname: Babbage
authors.forename: Richard
authors.initials: R
authors.lastname: Garand
authors.forename: Nelly
authors.initials: N
authors.lastname: Robillard
authors.forename: Niklas
authors.initials: N
authors.lastname: Zojer
authors.forename: Freda K
authors.initials: FK
authors.lastname: Stevenson
authors.forename: Surinder S
authors.initials: SS
authors.lastname: Sahota
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D003564:Cytidine Deaminase / Q000235:genetics*; D017931:DNA Primers; D005803:Genes, Immunoglobulin; D014644:Genetic Variation; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D020522:Lymphoma, Mantle-Cell / Q000235:genetics* / Q000276:immunology*; D008969:Molecular Sequence Data; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014178:Translocation, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D017931:DNA Primers; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase