1. ¹Institute for Genetics, Department of Immunology, Universität zu Köln, Köln, Frankfurt, Germany
2. ²Department for Internal Medicine I, Universität zu Köln, Köln, Frankfurt, Germany
3. ³Department of Pathology, University of Frankfurt, Frankfurt, Germany

Correspondence: Dr. Markus Müschen, Universität zu Köln, Institut für Genetik, LFI Gebäude E4 R705, Joseph-Stelzmann-Strae 9, 50931 Köln, Germany. E-mail: markus.mueschen@uni-koeln.de

Received 10 August 2000.

Abstract

Hodgkin- and Reed-Sternberg (H/RS) cells in classical Hodgkin's disease of the B lineage are the clonal progeny of antigen-experienced B cells harboring highly mutated immunoglobulin variable (V) region genes. Based on the detection of obviously destructive somatic mutations in a fraction of cases, we speculated that H/RS cells may be derived from a pre-apoptotic germinal center B cell. Seemingly contradicting this speculation, we present here the first case of classical Hodgkin's disease with H/RS cells harboring unmutated, potentially functional V region genes, which may indicate the derivation of the H/RS clone from a naive B cell. However, germinal center founder cells, which have not yet acquired somatic mutations, already have the intrinsic propensity to die by apoptosis. Thus, the rare occurrence of H/RS cells with unmutated V genes is expected if the H/RS cells are derived from the pool of pre-apoptotic germinal center B cells.