Expression of the interferon regulatory factor 8/ICSBP-1 in human reactive lymphoid tissues and B-cell lymphomas: a novel germinal center marker.
To assess the role of interferon regulatory factor (IRF) 8 in B-cell development and lymphomagenesis, we studied its expression in reactive lymphoid tissues, its relationship to other B-cell transcription factors, and its expression in a series of 232 B-cell tumors and 30 cell lines representing a variety of B-cell developmental stages. We found that although IRF8 was detectable in most reactive B-cells, its expression levels differed with developmental stage. Germinal center B cells contained the highest levels of IRF8, with lower levels seen in mantle and marginal zone B cells and none in plasma cells. IRF8 was coexpressed with PAX-5, Pu.1, and B-cell lymphoma (BCL)-6, and similar to BCL-6, was absent from the small population of IRF4-positive germinal center B cells thought to be committed to postgerminal center developmental programs. Similarly, IRF8 was most strongly expressed in lymphomas of germinal center origin with lower levels present in mantle cell lymphomas, chronic lymphocytic leukemia, and marginal zone lymphomas, and no expression observed in plasmacytic/plasmablastic neoplasms. The reciprocal expression pattern with IRF4 in reactive tissues was generally maintained in lymphomas with some exceptions. These results suggest an important role for IRF8 during germinal center B-cell development and in related lymphomas, and provide a new diagnostic marker helpful in distinguishing B-cell non-Hodgkin lymphoma subtypes.
Martinez
Antonio
A
Hematopathology Section, Laboratory of Pathology, National Cancer Institute, Bethesda, MD 20892, USA.
Pittaluga
Stefania
S
Rudelius
Martina
M
Davies-Hill
Theresa
T
Sebasigari
Denise
D
Fountaine
Thomas J
TJ
Hewitt
Stephen
S
Jaffe
Elaine S
ES
Raffeld
Mark
M
D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism; D003937:Diagnosis, Differential; D018858:Germinal Center / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D050835:Interferon Regulatory Factors / Q000378:metabolism*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000378:metabolism* / Q000473:pathology; D018442:Lymphoma, B-Cell, Marginal Zone / Q000378:metabolism; D020522:Lymphoma, Mantle-Cell / Q000378:metabolism; D051757:PAX5 Transcription Factor / Q000378:metabolism; D014066:Palatine Tonsil / Q000737:chemistry; D010950:Plasma Cells / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6; D015534:Trans-Activators / Q000378:metabolism; D000099185:Interferon Regulatory Factor-8; D000099232:Proto-Oncogene Protein Spi-1; D000099218:Interferon Regulatory Factor-4
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D051757:PAX5 Transcription Factor; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D015534:Trans-Activators; D000099185:Interferon Regulatory Factor-8; D000099232:Proto-Oncogene Protein Spi-1; D000099218:Interferon Regulatory Factor-4; C084103:BCL6 protein, human; C497281:PAX5 protein, human