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Blood, Vol. 92 No. 10 (November 15), 1998:
pp. 3857-3864
VH Gene Analysis of Primary Cutaneous B-Cell Lymphomas: Evidence for
Ongoing Somatic Hypermutation and Isotype Switching
W.M. Aarts,
R. Willemze,
R.J. Bende,
C.J.L.M. Meijer,
S.T. Pals, and
C.J.M. van Noesel
From the Department of Pathology, Academic Medical Center, Amsterdam,
The Netherlands; and the Departments of Dermatology and Pathology, Free
University Hospital, Amsterdam, The Netherlands.
Primary cutaneous B-cell lymphomas are B-cell non-Hodgkin's
lymphomas that arise in the skin. The major subtypes discerned are
follicle center cell lymphomas, immunocytomas (marginal zone B-cell
lymphomas), and large B-cell lymphomas of the leg. In this study, we
analyzed the variable heavy chain (VH) genes of 7 of these lymphomas,
ie, 4 follicle center cell lymphomas (diffuse large-cell lymphomas) and
3 immunocytomas. We show that all these lymphomas carry heavily mutated
VH genes, with no obvious bias in VH gene usage. The low ratios of
replacement versus silent mutations observed in the framework regions
of 5 of the 7 lymphomas suggest that the structure of the B-cell
antigen receptor was preserved, as in normal B cells that are selected
for antibody expression. Moreover, evidence for ongoing mutation was
obtained in 3 immunocytomas and in one lymphoma of large-cell type. In addition, in 1 immunocytoma, both IgG- and IgA-expressing clones were
found, indicative of isotype switching. Our data provide insight into
the biology of primary cutaneous B-cell lymphomas and may be of
significance for their classification.
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