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.
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 V(H) 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. (Blood. 2000;95:2084-2092)
Falini
B
B
Institutes of Hematology and Internal Medicine, University of Perugia, Perugia, Italy. faliniem@unipg.it
Fizzotti
M
M
Pucciarini
A
A
Bigerna
B
B
Marafioti
T
T
Gambacorta
M
M
Pacini
R
R
Alunni
C
C
Natali-Tanci
L
L
Ugolini
B
B
Sebastiani
C
C
Cattoretti
G
G
Pileri
S
S
Dalla-Favera
R
R
Stein
H
H
D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D000090266:Chromobox Protein Homolog 5; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000939:Epitopes; D006367:HeLa Cells; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000378:metabolism; D007150:Immunohistochemistry; D050835:Interferon Regulatory Factors; D019169:Jurkat Cells; D008198:Lymph Nodes / Q000378:metabolism; D008223:Lymphoma / Q000378:metabolism; D009101:Multiple Myeloma / Q000378:metabolism; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D000099218:Interferon Regulatory Factor-4
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D000090266:Chromobox Protein Homolog 5; D004268:DNA-Binding Proteins; D000939:Epitopes; D007135:Immunoglobulin Variable Region; D050835:Interferon Regulatory Factors; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D000099218:Interferon Regulatory Factor-4; C000715594:CBX5 protein, human