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Blood, 1 April 2002, Vol. 99, No. 7, pp. 2562-2568
NEOPLASIA
Acquisition of potential N-glycosylation sites in the
immunoglobulin variable region by somatic mutation is a distinctive
feature of follicular lymphoma
Delin Zhu,
Helen McCarthy,
Christian H. Ottensmeier,
Peter Johnson,
Terry J. Hamblin, and
Freda K. Stevenson
From the Molecular Immunology Group, Tenovus
Laboratory, and the CRC Medical Oncology Unit, Cancer Sciences
Division, Southampton University Hospitals Trust, United Kingdom.
Most patients with follicular lymphoma (FL) have somatically
mutated V genes with intraclonal variation, consistent with
location in the germinal center site. Using our own and published
sequences, we have investigated the frequency of potential
N-glycosylation sites introduced into functional VH genes
as a consequence of somatic mutation. FL cells were compared with
normal memory B cells or plasma cells matched for similar levels of
mutation. Strikingly, novel sites were detected in 55 of 70 (79%)
patients with FL, compared to 7 of 75 (9%) in the normal B-cell
population (P < .001). Diffuse large B-cell lymphoma
(DLCL) showed an intermediate frequency (13 of 32 [41%] patients).
Myeloma and the mutated subset of chronic lymphocytic leukemia showed
frequencies similar to those of normal cells in 5 of 64 (8%) patients
and 5 of 40 (13%) patients, respectively. In 3 of 3 random patients
with FL, immunoglobulin was expressed as recombinant single-chain Fv in
Pichia pastoris, and glycosylation was demonstrated. These
findings indicate that N-glycosylation of the variable region may be
common in FL and in a subset of DLCL. Most novel sites are located in
the complementarity-determining regions. VH sequences of
nonfunctional VH genes contained few sites, arguing for
positive selection in FL. One possibility is that the added
carbohydrate in the variable region contributes to interaction with
elements in the germinal center environment. This common feature of FL
may be critical for tumor behavior.
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