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Ongoing Ig gene hypermutation in salivary gland mucosa-associated lymphoid
tissue-type lymphomas
DW Bahler, JA Miklos and SH Swerdlow
Department of Pathology, University of Pittsburgh School of Medicine, PA,
USA.
Salivary gland mucosa-associated lymphoid tissue (MALT) type lymphomas are
typically indolent B-cell neoplasms that are often associated with
Sjogren's syndrome. To better define the cell of origin and evaluate
whether antigen receptor stimulation may be playing a role in tumor growth,
the Ig heavy and light chain variable genes (VH and VL) expressed by five
salivary gland MALT lymphomas were cloned and sequenced. Comparison to
known germline sequences indicated that three of the lymphoma VH genes were
derived from 51p1, a member of the VH1 family, while the other two used
different VH gene segments from the VH3 family, 22-2B and HG19. All five of
the VL genes belonged to the VkIII family, with three derived from Humkv325
and the other two from the Vg and Humkv328 genes. Numerous point mutations
relative to the proposed germline genes were present in all of the lymphoma
VH and VL genes. In addition, the VH and VL genes from each lymphoma showed
intraclonal sequence heterogeneity indicative of ongoing somatic
hypermutation. Because the process of Ig gene hypermutation is thought to
occur at the germinal center stage of B-cell development, these findings
suggest the MALT lymphoma cell of origin may be a germinal center B cell.
Selection against mutations that result in replacement of amino acids
suggested that Ig stimulation may be important for lymphoma growth. The
possibility that antigen receptor stimulation may be involved in the growth
of salivary gland MALT lymphomas is further suggested by the noted
restricted use of VH and VL gene segments.
Volume 89,
Issue 9,
pp. 3335-3344,
05/01/1997
Copyright © 1997 by The American Society of Hematology
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