Published 18 April 2005. doi:10.1084/jem.20050068
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 8, 1229-1241
Among B cell non-Hodgkin's lymphomas, MALT lymphomas express a unique antibody repertoire with frequent rheumatoid factor reactivity
Richard J. Bende1,
Wilhelmina M. Aarts1,
Robert G. Riedl1,
Daphne de Jong2,
Steven T. Pals1, and
Carel J.M. van Noesel1
1 Department of Pathology, Academic Medical Center
2 Department of Pathology, Netherlands Cancer Institute, 1105 AZ Amsterdam, Netherlands
CORRESPONDENCE Carel J.M. van Noesel: c.j.vannoesel{at}amc.uva.nl
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)VH-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 IgVH 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.
Abbreviations used: Ag, antigen; B-CLL, B cell chronic lymphocytic leukemia; B-NHL, B non-Hodgkin's lymphoma; BCR, B cell antigen receptor; BL, Burkitt's lymphoma; D, diversity; DLBCL, diffuse large B cell lymphoma; FL, follicular lymphoma; FR, framework region; GC, germinal center; HCV, hepatitis C virus; HID, healthy immunized donor; ICV, intraclonal sequence variation; J, joining; LIDA lymphoma- idiotype-derived Ab; MALT, mucosa-associated lymphoid tissue; MCL, mantle cell lymphoma; MZBCL, marginal zone B cell lymphoma; RF, rheumatoid factor; V, variable.
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