Among B cell non-Hodgkin's lymphomas, MALT lymphomas express a unique antibody repertoire with frequent rheumatoid factor reactivity.
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.
Bende
Richard J
RJ
Department of Pathology, Academic Medical Center, Netherlands Cncer Institute, 1105 AZ Amsterdam, The Netherlands.
Aarts
Wilhelmina M
WM
Riedl
Robert G
RG
de Jong
Daphne
D
Pals
Steven T
ST
van Noesel
Carel J M
CJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000912:Antibodies, Neoplasm / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D022801:Complementarity Determining Regions; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000737:chemistry / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000276:immunology*; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012217:Rheumatoid Factor / Q000737:chemistry / Q000276:immunology*; D017386:Sequence Homology, Amino Acid
D000912:Antibodies, Neoplasm; D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D012217:Rheumatoid Factor