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Hodgkin's disease with a B-cell phenotype often shows a VDJ rearrangement
and somatic mutations in the VH genes
J Tamaru, M Hummel, M Zemlin, B Kalvelage and H Stein
Consultation and Reference Centre for Lymph Node Pathology and
Hematopathology, Free University Berlin, Germany.
The nature of Hodgkin and Reed-Sternberg (HRS) cells remains in question.
Immunophenotypic studies favor a relation to the lymphoid lineage with the
existence of B- and T-cell types. However, studies on the detection of
antigen (Ag) receptor gene rearrangements provided inconsistent results.
They concur in that rearranged Ig and T-cell receptor (TCR) genes are not
demonstrable in most Hodgkin's disease (HD) cases. To clarify whether this
is because of the insensitivity of the method of detection or a real
absence of clonal Ig heavy chain (IgH) rearrangements, a polymerase chain
reaction (PCR) method with high sensitivity was applied, allowing the
detection of less than 50 cells with clonally rearranged IgH genes in a
mixture of 100,000 germline or individually rearranged cells. In 67 cases
of HD, most of those (67%) with B-Ag+ HRS cells express clonal VDJ
rearrangements of the IgH gene. No cases with T-cell Ag+ HRS cells harbored
detectable clonal VDJ rearrangements. Of 10 sequenced rearranged IgH genes,
the VH segment of six contained considerable somatic mutations. These
results suggest that the demonstrated VDJ rearrangements stem from the HRS
cells themselves and that the HRS cells of cases with rearranged IgH genes
are B-cell related and correspond in their differentiation stage either to
naive pregerminal center B cells or (more commonly) to germinal
center/postgerminal center-derived memory B cells.
Volume 84,
Issue 3,
pp. 708-715,
08/01/1994
Copyright © 1994 by The American Society of Hematology
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