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Annals of Oncology 8:S79-S81, 1997
© 1997 European Society for Medical Oncology

Normal and malignant B-cell development with special reference to Hodgkin's disease

K. Rajewsky1, H. Kanzler1, M.-L. Hansmann1,2 and R. Küppers1

1 Institute for Genetics and Development for Pathology, University of Cologne Cologne
2 Senckenbergisches Zentrum der Pathologie, University of Frankfurt Frankfurt, Germany

Correspondence to: Dr. Klaus Rajewsky Institute for Genetics University of Cologne Weyertal 121 50931 Cologne Germany

During their development, B lymphocytes are repeatedly selected for the expression of an appropriate surface receptor: the pre-B-cell receptor at the pre-B-cell stage and surface immuno-globulin (Ig) at the transition from a pre-B cell to a mature B cell. Furthermore, stringent selection for B cells expressing high affinity antibodies operates when antigen-activated B cells proliferate within germinal centers (GC). Here, somatic point mutations are introduced into rearranged V region genes at a high rate, and B cells acquiring favorable mutations are selected to differentiate into memory B cells or plasma cells.

In the frame of this developmental scheme, extending a recent analysis, we investigated 10 primary cases of Hodgkin's disease (HD) for B-lineage origin and clonality [1]. Single Hodgkin and Reed-Sternberg (H-RS) cells were micromanipulated from frozen tissue sections and analyzed by PCR for rearranged V genes. Clonal VH and/or V{kappa}/V{lambda} gene rearrangements were obtained from 9 of the cases. This shows that H-RS cells represent a clonal, B-lineage-derived population of tumor cells. Somatic mutations were found in all clonal VH gene rearrangements. Interestingly, mutations leading to stop codons in in-frame V gene rearrangements were detected in four cases. Since GC B cells acquiring such crippling mutations are usually efficiently eliminated within the GC, the finding of those mutations indicates that H-RS cells are derived from precursors within the GC that escaped apoptosis by a transforming event.

germinal center, Hodgkin's disease, Ig gene rearrangement, micromanipulation, Reed-Sternberg cell, single-cell PCR


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