Abstract
We analyzed the structure of antigen receptors of a comprehensive panel of mature B non-Hodgkin's lymphomas (B-NHLs) by comparing, at the amino acid level, their immunoglobulin (Ig)V(H)-CDR3s with CDR3 sequences present in GenBank. Follicular lymphomas, diffuse large B cell lymphomas, Burkitt's lymphomas, and myelomas expressed a CDR3 repertoire comparable to that of normal B cells. Mantle cell lymphomas and B cell chronic lymphocytic leukemias (B-CLLs) expressed clearly restricted albeit different CDR3 repertoires. Lymphomas of mucosa-associated lymphoid tissues (MALTs) were unique as 8 out of 45 (18%) of gastric- and 13 out of 32 (41%) of salivary gland-MALT lymphomas expressed B cell antigen receptors with strong CDR3 homology to rheumatoid factors (RFs). Of note, the RF-CDR3 homology without exception included N-region-encoded residues in the hypermutated IgV(H) genes, indicating that they were stringently selected for reactivity with auto-IgG. By in vitro binding studies with 10 MALT lymphoma-derived antibodies, we showed that seven of these cases, of which four with RF-CDR3 homology, indeed possessed strong RF reactivity. Of one MALT lymphoma, functional proof for selection of subclones with high RF affinity was obtained. Interestingly, RF-CDR3 homology and t(11;18) appeared to be mutually exclusive features and RF-CDR3 homology was not encountered in any of the 19 pulmonary MALT lymphomas studied.
MeSH terms
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Adult
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Aged
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Aged, 80 and over
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Amino Acid Sequence
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Antibodies, Neoplasm / biosynthesis*
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Antibodies, Neoplasm / chemistry
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Antibodies, Neoplasm / genetics
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Complementarity Determining Regions
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Female
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Humans
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Immunoglobulin Heavy Chains / chemistry
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Immunoglobulin Heavy Chains / genetics
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Immunoglobulin Light Chains / chemistry
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Immunoglobulin Light Chains / genetics
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Lymphoma, B-Cell / genetics
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Lymphoma, B-Cell / immunology*
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Lymphoma, B-Cell, Marginal Zone / genetics
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Lymphoma, B-Cell, Marginal Zone / immunology*
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Male
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Middle Aged
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Molecular Sequence Data
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Reverse Transcriptase Polymerase Chain Reaction
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Rheumatoid Factor / chemistry
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Rheumatoid Factor / immunology*
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Sequence Homology, Amino Acid
Substances
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Antibodies, Neoplasm
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Complementarity Determining Regions
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Immunoglobulin Heavy Chains
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Immunoglobulin Light Chains
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Rheumatoid Factor
Associated data
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GENBANK/AY281324
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GENBANK/AY281325
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GENBANK/AY281326
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GENBANK/AY281327
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GENBANK/AY281328
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GENBANK/AY281329
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GENBANK/AY281330
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GENBANK/AY281331
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GENBANK/AY281332
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GENBANK/AY281333
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GENBANK/AY281334
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GENBANK/AY281335
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GENBANK/AY281336
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GENBANK/AY281337
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GENBANK/AY281338
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GENBANK/AY281339
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GENBANK/AY281340
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GENBANK/AY281341
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GENBANK/AY281342
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GENBANK/AY281343
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GENBANK/AY466502
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GENBANK/AY466503
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GENBANK/AY561708
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GENBANK/AY927657
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GENBANK/AY927658
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GENBANK/AY927659
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GENBANK/AY927660
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GENBANK/AY927661
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GENBANK/AY927662
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GENBANK/AY927663
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GENBANK/AY927664
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GENBANK/AY927665
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GENBANK/AY927666
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GENBANK/AY927667
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GENBANK/AY927668