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Clonality in nodular lymphocyte-predominant Hodgkin's disease. 1997

T Ohno, and J A Stribley, and G Wu, and S H Hinrichs, and D D Weisenburger, and W C Chan
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-3135, USA.

BACKGROUND There is general agreement that lymphocytic and histiocytic (L&H) cells, the variants of Reed-Sternberg cells in nodular lymphocyte-predominant Hodgkin's disease, belong to the B-cell lineage. However, the clonality of L&H cells remains controversial. METHODS We used complementarity-determining region 3 (CDR3) of the immunoglobulin heavy-chain gene as a clonal marker to study individual L&H cells isolated by micromanipulation from tissue sections of five patients with nodular lymphocyte-predominant Hodgkin's disease. The heavy-chain CDR3 of each cell was amplified by the polymerase chain reaction. The products were analyzed by gel electrophoresis, and representative amplification products from each patient were sequenced. RESULTS L&H cells whose heavy-chain CDR3 was related, indicating the presence of a clonal population, were detected in all five patients and were the dominant population in three. In four of the five patients, members of the clone were found in different nodules in the tissue section, different tissue blocks from the same tumor, or different lymph nodes from the same patient. The CDR3 sequences in each clone frequently contained nucleotide substitutions indicative of intraclonal mutation. CONCLUSIONS Clonal populations of L&H cells occur in nodular lymphocyte-predominant Hodgkin's disease. Intraclonal variation in nucleotide sequences suggests that hypermutation of the heavy-chain CDR3 continues to occur among the clonal progeny.

UI MeSH Term Description Entries
D007135 Immunoglobulin Variable Region That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions. Variable Region, Ig,Variable Region, Immunoglobulin,Framework Region, Immunoglobulin,Fv Antibody Fragments,Fv Fragments,Ig Framework Region,Ig Variable Region,Immunoglobulin Framework Region,Immunoglobulin Fv Fragments,Immunoglobulin V,Antibody Fragment, Fv,Antibody Fragments, Fv,Fragment, Fv,Fragment, Fv Antibody,Fragment, Immunoglobulin Fv,Fragments, Fv,Fragments, Fv Antibody,Fragments, Immunoglobulin Fv,Framework Region, Ig,Framework Regions, Ig,Framework Regions, Immunoglobulin,Fv Antibody Fragment,Fv Fragment,Fv Fragment, Immunoglobulin,Fv Fragments, Immunoglobulin,Ig Framework Regions,Ig Variable Regions,Immunoglobulin Framework Regions,Immunoglobulin Fv Fragment,Immunoglobulin Variable Regions,Regions, Immunoglobulin Variable,Variable Regions, Ig,Variable Regions, Immunoglobulin
D007143 Immunoglobulin Heavy Chains The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kDa. Immunoglobulins, Heavy-Chain,Heavy-Chain Immunoglobulins,Ig Heavy Chains,Immunoglobulin Heavy Chain,Immunoglobulin Heavy Chain Subgroup VH-I,Immunoglobulin Heavy Chain Subgroup VH-III,Heavy Chain Immunoglobulins,Heavy Chain, Immunoglobulin,Heavy Chains, Ig,Heavy Chains, Immunoglobulin,Immunoglobulin Heavy Chain Subgroup VH I,Immunoglobulin Heavy Chain Subgroup VH III,Immunoglobulins, Heavy Chain
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D002999 Clone Cells A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed) Clones,Cell, Clone,Cells, Clone,Clone,Clone Cell
D005803 Genes, Immunoglobulin Genes encoding the different subunits of the IMMUNOGLOBULINS, for example the IMMUNOGLOBULIN LIGHT CHAIN GENES and the IMMUNOGLOBULIN HEAVY CHAIN GENES. The heavy and light immunoglobulin genes are present as gene segments in the germline cells. The completed genes are created when the segments are shuffled and assembled (B-LYMPHOCYTE GENE REARRANGEMENT) during B-LYMPHOCYTE maturation. The gene segments of the human light and heavy chain germline genes are symbolized V (variable), J (joining) and C (constant). The heavy chain germline genes have an additional segment D (diversity). Genes, Ig,Immunoglobulin Genes,Gene, Ig,Gene, Immunoglobulin,Ig Gene,Ig Genes,Immunoglobulin Gene
D006689 Hodgkin Disease A malignant disease characterized by progressive enlargement of the lymph nodes, spleen, and general lymphoid tissue. In the classical variant, giant usually multinucleate Hodgkin's and REED-STERNBERG CELLS are present; in the nodular lymphocyte predominant variant, lymphocytic and histiocytic cells are seen. Granuloma, Hodgkin,Granuloma, Malignant,Hodgkin Lymphoma,Lymphogranuloma, Malignant,Granuloma, Hodgkin's,Granuloma, Hodgkins,Hodgkin Lymphoma, Adult,Hodgkin's Disease,Hodgkin's Lymphoma,Hodgkins Disease,Lymphocyte Depletion Hodgkin's Lymphoma,Lymphocyte-Rich Classical Hodgkin's Lymphoma,Mixed Cellularity Hodgkin's Lymphoma,Nodular Lymphocyte-Predominant Hodgkin's Lymphoma,Nodular Sclerosing Hodgkin's Lymphoma,Adult Hodgkin Lymphoma,Disease, Hodgkin,Disease, Hodgkin's,Disease, Hodgkins,Hodgkin Granuloma,Hodgkin's Granuloma,Hodgkins Granuloma,Hodgkins Lymphoma,Lymphocyte Rich Classical Hodgkin's Lymphoma,Lymphogranulomas, Malignant,Lymphoma, Hodgkin,Lymphoma, Hodgkin's,Malignant Granuloma,Malignant Granulomas,Malignant Lymphogranuloma,Malignant Lymphogranulomas,Nodular Lymphocyte Predominant Hodgkin's Lymphoma
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001402 B-Lymphocytes Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B-Cells, Lymphocyte,B-Lymphocyte,Bursa-Dependent Lymphocytes,B Cells, Lymphocyte,B Lymphocyte,B Lymphocytes,B-Cell, Lymphocyte,Bursa Dependent Lymphocytes,Bursa-Dependent Lymphocyte,Lymphocyte B-Cell,Lymphocyte B-Cells,Lymphocyte, Bursa-Dependent,Lymphocytes, Bursa-Dependent
D001483 Base Sequence The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence. DNA Sequence,Nucleotide Sequence,RNA Sequence,DNA Sequences,Base Sequences,Nucleotide Sequences,RNA Sequences,Sequence, Base,Sequence, DNA,Sequence, Nucleotide,Sequence, RNA,Sequences, Base,Sequences, DNA,Sequences, Nucleotide,Sequences, RNA
D016133 Polymerase Chain Reaction In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. Anchored PCR,Inverse PCR,Nested PCR,PCR,Anchored Polymerase Chain Reaction,Inverse Polymerase Chain Reaction,Nested Polymerase Chain Reaction,PCR, Anchored,PCR, Inverse,PCR, Nested,Polymerase Chain Reactions,Reaction, Polymerase Chain,Reactions, Polymerase Chain

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