Background There is general agreement that lymphocytic and histiocytic(L&H) cells, the variants of Reed–Sternberg cellsin nodular lymphocyte-predominant Hodgkin's disease, belongto the B-cell lineage. However, the clonality of L&H cellsremains controversial.
Methods We used complementarity-determining region 3 (CDR3)of the immunoglobulin heavy-chain gene as a clonal marker tostudy individual L&H cells isolated by micromanipulationfrom tissue sections of five patients with nodular lymphocyte-predominantHodgkin's disease. The heavy-chain CDR3 of each cell was amplifiedby the polymerase chain reaction. The products were analyzedby gel electrophoresis, and representative amplification productsfrom each patient were sequenced.
Results L&H cells whose heavy-chain CDR3 was related, indicatingthe presence of a clonal population, were detected in all fivepatients and were the dominant population in three. In fourof the five patients, members of the clone were found in differentnodules in the tissue section, different tissue blocks fromthe same tumor, or different lymph nodes from the same patient.The CDR3 sequences in each clone frequently contained nucleotidesubstitutions indicative of intraclonal mutation.
Conclusions Clonal populations of L&H cells occur in nodularlymphocyte-predominant Hodgkin's disease. Intraclonal variationin nucleotide sequences suggests that hypermutation of the heavy-chainCDR3 continues to occur among the clonal progeny.
Source Information
Presented in abstract form at the Annual Meeting of the American Society of Hematology, Orlando, Fla., December 6–10, 1996.
From the Department of Pathology and Microbiology, University of Nebraska Medical Center, 600 S. 42nd St., P.O. Box 983135, Omaha, NE 68198-3135, where reprint requests should be addressed to Dr. Chan.
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