The cellular origin of H-RS cells has been questioned for a long time.
Recently, using single cell amplification of Ig genes evidence was ob
tained that H-RS cells clonally arise from B-cells. Sequence analysis
of rearranged Ig genes demonstrated that H-RS cells develop within the
germinal centre. H-RS cells in classical KD grow despite loss of func
tion of their rearranged Ig genes. In contrast, the mutation pattern o
f rearranged Ig genes in L & H cells of lymphocyte-predominant HD freq
uently shows ongoing mutations indicating that these cell are still an
tigen selected. These molecular differences show that LP HD geneticall
y differs from classical HD. H-RS cells escape from apoptosis within t
he germinal centre. However, the events leading to malignant transform
ation are still unknown. The association between EBV and HD has been r
epeatedly described, but the occurrence of EBV negative cases is hard
to explain just by loss of EBV. The analysis of chromosomal aberration
s in H-RS cells did not result in the description of a specific 'HD-ge
ne'. Also the role of the T-lymphocytes surrounding the H-RS cells has
remained an open question. (C) 1997 John Wiley & Sons, Ltd.