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Analysis of VH genes used by neoplastic B cells in endemic Burkitt's
lymphoma shows somatic hypermutation and intraclonal heterogeneity
CJ Chapman, CI Mockridge, M Rowe, AB Rickinson and FK Stevenson
Tenovus Laboratory, Southampton University Hospitals, UK.
Tumor cell lines from six typical cases of endemic Epstein-Barr virus (EBV)
genome-positive Burkitt's lymphoma (BL) have been investigated for usage
and mutational pattern of Ig VH genes. The neoplastic cells all had a
t(8;14) (q24;q32) translocation involving the c-myc protooncogene. The VH
genes were derived from VH1, VH3 and VH4, and both the IgM-positive (four
cases) and IgG-positive (two cases) were extensively mutated from germline
sequence. In two cases, early and late passage tumor cells were available,
and the VH nucleotide sequences were identical, indicating that mutations
had not accumulated in vitro. In a further case, there was evidence of
sequence heterogeneity, which appeared to have been generated in vivo,
indicating that the tumor cell VH gene was able to undergo
posttranslocation somatic hypermutation. Analysis of the relatively
nonpolymorphic VH4 genes for the pattern of replacement or silent mutations
did not show a role for antigen selection in the expressed sequences.
Volume 85,
Issue 8,
pp. 2176-2181,
04/15/1995
Copyright © 1995 by The American Society of Hematology
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