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Blood, Vol. 95 No. 6 (March 15), 2000:
pp. 2084-2092
A monoclonal antibody (MUM1p) detects expression of the MUM1/IRF4
protein in a subset of germinal center B cells, plasma cells, and
activated T cells
Brunangelo Falini,
Marco Fizzotti,
Alessandra Pucciarini,
Barbara Bigerna,
Teresa Marafioti,
Marcello Gambacorta,
Roberta Pacini,
Cristina Alunni,
Laura Natali-Tanci,
Barbara Ugolini,
Carla Sebastiani,
Giorgio Cattoretti,
Stefano Pileri,
Riccardo Dalla-Favera, and
Harald Stein
From the Institutes of Hematology and Internal Medicine, University
of Perugia, Perugia; the Institute of Pathology, Niguarda Hospital,
Milan, Italy; the Institute of Pathology, University of Bologna,
Bologna, Italy; the Department of Pathology, College of Physicians and
Surgeons, Columbia University, New York, NY; and the Institute of
Pathology, Benjamin Franklin University, Berlin, Germany.
A new monoclonal antibody (MUM1p) was used to study the cell/tissue
expression of human MUM1/IRF4 protein, the product of the homologous
gene involved in the myeloma-associated t(6;14) (p25;q32). MUM1 was
expressed in the nuclei and cytoplasm of plasma cells and a small
percentage of germinal center (GC) B cells mainly located in the
"light zone." Its morphologic spectrum ranged from that of
centrocyte to that of a plasmablast/plasma cell, and it displayed a
phenotype
(MUM1+/Bcl-6 /Ki67)
different from that of most GC B cells
(MUM1/Bcl-6+/Ki67+) and
mantle B cells
(MUM1/Bcl-6/Ki67).
Polymerase chain reaction (PCR) analysis of single MUM1+
cells isolated from GCs showed that they contained rearranged Ig
heavy chain genes with a varying number of VH
somatic mutations. These findings suggest that these cells may
represent surviving centrocytes and their progeny committed to exit GC
and to differentiate into plasma cells. MUM1 was strongly expressed in
lymphoplasmacytoid lymphoma, multiple myeloma, and approximately 75%
of diffuse large B-cell lymphomas (DLCL-B). Unlike normal GC B cells,
in which the expression of MUM1 and Bcl-6 were mutually exclusive,
tumor cells in approximately 50% of MUM1+ DLCL-B
coexpressed MUM1 and Bcl-6, suggesting that expression of these
proteins may be deregulated. In keeping with their proposed origin from
GC B cells, Hodgkin and Reed-Sternberg cells of Hodgkin's disease
consistently expressed MUM1. MUM1 was detected in normal and neoplastic
activated T cells, and its expression usually paralleled that of CD30.
These results suggest that MUM1 is involved in the late stages of
B-cell differentiation and in T-cell activation and is deregulated in
DLCL-B.
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