Background There is strong evidence that ReedSternbergcells have a lymphoid phenotype, but clonally rearranged genesfor B-cell and T-cell antigen receptors have not been demonstrablein tumor tissue from most patients with Hodgkin's disease. Toelucidate this issue, we assayed single ReedSternbergcells from 12 patients with classic Hodgkin's disease of a B-cellimmunophenotype to detect rearranged immunoglobulin variable-regionheavy-chain (Vh) genes.
Methods We isolated single ReedSternberg cells from frozensections that had been immunostained for CD30. The rearrangedVh genes of these cells were amplified by the polymerase chainreaction and analyzed by gel electrophoresis and nucleotidesequencing.
Results In all 12 patients, the ReedSternberg cells studiedcontained rearranged Vh genes. Three patterns were observed:in three patients the rearrangements in each patient were identical,in six patients all the rearrangements were unrelated and unique,and in three patients both identical and unrelated rearrangementswere detected. Apparently somatic mutations of Vh genes werepresent in some Reedsternberg cells but absent in others.
Conclusions ReedSternberg cells with B-cell phenotypeshave rearranged Vh genes; therefore, these cells arise fromB cells. The pattern of Vh gene mutations suggests that ReedSternbergcells can correspond to either immunologically naive or memoryB cells. In half our patients the population of ReedSternbergcells was polyclonal; in the other half, monoclonal or mixedcell populations were found. Correlation with the clinical stagesuggests that polyclonal Hodgkin's disease can present as awidespread lymphoma.
Source Information
From the Institute of Pathology, Klinikum Benjamin Franklin, Freie Universität Berlin, Berlin, Germany (M.H., K.Z., H.L., H.S.); and the Hematopathology Unit, Second Service of Pathological Anatomy, University of Bologna, Bologna, Italy (S.P., E.S.).
Address reprint requests to Professor Stein at the Institute of Pathology, Klinikum Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, 12200 Berlin, Germany.
Immunoglobulin V Genes in ReedSternberg Cells
Küppers R., Kanzler H., Hansmann M.-L., Rajewsky K., Trümper L., Daus H., Gause A., Pfreundschuh M., Tbakhi A., Sreenan J., Tubbs R. R., Hummel M., Marafioti T., Stein H.
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N Engl J Med 1996;
334:404-406, Feb 8, 1996.
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