Clonality and germinal centre B-cell derivation of Hodgkin/Reed–Sternberg cells in Hodgkin’s disease

Abstract

Molecular single-cell studies of Hodgkin and Reed-Sternberg (HRS) cells in Hodgkin's disease (HD) have revealed the clonal nature of these peculiar tumour cells. HRS cells in classical HD as well as lymphocyte predominant (LP) HD originate from germinal center (GC) B cells in most cases, if not all. Whereas HRS cells in LP HD represent transformed antigen-selected GC B cells with evidence of ongoing immunoglobulin (Ig) V gene mutation, HRS cells in classical HD appear to often or always derive from GC B cells that have lost the capacity to express a functional antigen receptor. Using Ig gene rearrangements amplified from HRS cells as clonal markers for the tumour cells, it could be shown that the same HRS cell clone can disseminate in the patient and persist throughout the course of the disease. A common derivation of the tumour cells was recently demonstrated in two cases representing combinations of HD and non-Hodgkin's lymphoma. Finally, V-gene analysis showed that viable cells enriched by magnetic cell sorting from HD patients as HRS cells indeed represent the HRS-cell population of the patient.