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Blood, 1 August 2001, Vol. 98, No. 3, pp. 781-786
NEOPLASIA
Nodal marginal zone B-cell lymphomas may arise from different
subsets of marginal zone B lymphocytes
Annarita Conconi,
Francesco Bertoni,
Ennio Pedrinis,
Teresio Motta,
Enrico Roggero,
Stefano Luminari,
Carlo Capella,
Marzia Bonato,
Franco Cavalli, and
Emanuele Zucca
From the Oncology Institute of Southern Switzerland,
Division of Medical Oncology, Bellinzona, Switzerland; Department of
Experimental Haematology, St Bartholomew's and The Royal London School
of Medicine and Dentistry, London, United Kingdom; Istituto Cantonale
di Patologia, Locarno, Switzerland; Anatomia Patologica e Citologia,
Ospedali Riuniti Bergamo, Italy; Servizio di Ematologia,
Università Statale di Milano, Ospedale Maggiore IRCCS, Milan,
Italy; and Istituto di Anatomia e Istologia Patologica,
Università dell'Insubria, Varese, Italy.
Nodal marginal zone B-cell lymphoma (MZL) is a rare and not
extensively studied entity that accounts for approximately 2% of all
non-Hodgkin lymphomas. Complementarity-determining regions 2 and 3 (CDR2, CDR3) of the immunoglobulin heavy-chain variable region
(VH) genes were amplified by polymerase chain reaction (PCR), cloned, and sequenced in 8 patients with nodal MZL. All showed a
potentially functional VH rearrangement. The use of
VH gene families was unbiased and without
overrepresentation of any particular VH gene or gene
family. The presence of somatic VH mutations was detected,
with a deviation from the closest germ line sequence ranging from 4%
to 17% in 6 of 8 patients. In 3 mutations, the replacement-to-silent
mutation ratio suggested the presence of an antigen-selected process.
Sequencing different subclones of the same cloned PCR products allowed
the detection of intraclonal variability in 4 analyzed patients. The
observed pattern of VH mutations suggested that nodal MZL,
formerly deemed a malignancy of memory B cells, may arise from
different subsets of marginal zone B cells the naive B cells that
express unmutated VH genesfrom memory B cells showing
somatic mutations without intraclonal variation, and from germinal
center B cells defined by their capacity to undergo the somatic
hypermutation process.
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