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Absence of immunoglobulin variable region hypermutation in a large cell
lymphoma after in vivo and in vitro propagation
N Stiernholm, B Kuzniar and NL Berinstein
Department of Medicine, University of Toronto, Ontario, Canada.
Several genetic mechanisms have been shown to diversity the expressed
antibody repertoire of committed B lymphocytes. These include somatic
hypermutation, V gene replacement, and ongoing gene rearrangement. These
mechanisms may be operational at discrete points in the B-cell
differentiation pathway and may generate idiotypic diversity in various
malignant B-cell tumors. Hypermutation of the Ig variable region has been
shown to occur in follicular lymphoma, but not in pre-B cell acute
lymphoblastic leukemia, Burkitt's lymphoma, chronic lymphocytic leukemia,
or myeloma. To study hypermutation in a large cell lymphoma, we use a
polymerase chain reaction-based approach, employing consensus VH and JH
primers, to clone and sequence rearranged Ig heavy chain variable regions.
Neither tumor cells immortalized in rescue fusions nor idiotypic variants
of a tumor-derived cell line generated through ongoing lambda light chain
gene rearrangements show any significant number of variable region
mutations. Thus, at the in vivo stage of B- cell differentiation from which
this large cell lymphoma arose, Ig variable region hypermutation was not
occurring, nor did it occur during propagation in vitro of these tumor
cells. Thus, the window of hypermutation in malignant B-cell tumors is more
precisely defined, which may have clinical implications for diagnostic and
therapeutic approaches directed at the Ig variable region.
Volume 80,
Issue 3,
pp. 738-743,
08/01/1992
Copyright © 1992 by The American Society of Hematology
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