The transit of T cell-activated B cells through the germinal center (GC) is controlled by sequential activation and repression of key transcription factors, executing the pre- and post-GC B cell program. B cell lymphoma (BCL) 6 and IFN regulatory factor (IRF) 8 are necessary for GC formation and for its molecular activity in Pax5+PU.1+ B cells. IRF4, which is highly expressed in BCL6- GC B cells, is necessary for class switch recombination and the plasma cell differentiation at exit from the GC. In this study, we show at the single-cell level broad coexpression of IRF4 with BCL6, Pax5, IRF8, and PU.1 in pre- and post-GC B cells in human and mouse. IRF4 is down-regulated in BCL6+ human GC founder cells (IgD+CD38+), is absent in GC centroblasts, and is re-expressed in positive regulatory domain 1-positive centrocytes, which are negative for all the B cell transcription factors. Activated (CD30+) and activation-induced cytidine deaminase-positive extrafollicular blasts coexpress Pax5 and IRF4. PU.1-negative plasma cells and CD30+ blasts uniquely display the conformational epitope of IRF4 recognized by the MUM1 Ab, an epitope that is absent from any other IRF4+PU.1+ lymphoid and hemopoietic subsets. Low grade B cell lymphomas, representing the malignant counterpart of pre- and post-GC B cells, accordingly express IRF4. However, a fraction of BCL6+ diffuse large B cell lymphomas express IRF4 bearing the MUM1 epitope, indicative of a posttranscriptional modification of IRF4 not seen in the normal counterpart.

Cattoretti, G., Shaknovich, R., Smith, P., Jäck, H., Murty, V., & Alobeid, B. (2006). Stages of germinal center transit are defined by B cell transcription factor coexpression and relative abundance. JOURNAL OF IMMUNOLOGY, 117(10), 6930-6939.

Stages of germinal center transit are defined by B cell transcription factor coexpression and relative abundance.

CATTORETTI, GIORGIO;
2006-11-15

Abstract

The transit of T cell-activated B cells through the germinal center (GC) is controlled by sequential activation and repression of key transcription factors, executing the pre- and post-GC B cell program. B cell lymphoma (BCL) 6 and IFN regulatory factor (IRF) 8 are necessary for GC formation and for its molecular activity in Pax5+PU.1+ B cells. IRF4, which is highly expressed in BCL6- GC B cells, is necessary for class switch recombination and the plasma cell differentiation at exit from the GC. In this study, we show at the single-cell level broad coexpression of IRF4 with BCL6, Pax5, IRF8, and PU.1 in pre- and post-GC B cells in human and mouse. IRF4 is down-regulated in BCL6+ human GC founder cells (IgD+CD38+), is absent in GC centroblasts, and is re-expressed in positive regulatory domain 1-positive centrocytes, which are negative for all the B cell transcription factors. Activated (CD30+) and activation-induced cytidine deaminase-positive extrafollicular blasts coexpress Pax5 and IRF4. PU.1-negative plasma cells and CD30+ blasts uniquely display the conformational epitope of IRF4 recognized by the MUM1 Ab, an epitope that is absent from any other IRF4+PU.1+ lymphoid and hemopoietic subsets. Low grade B cell lymphomas, representing the malignant counterpart of pre- and post-GC B cells, accordingly express IRF4. However, a fraction of BCL6+ diffuse large B cell lymphomas express IRF4 bearing the MUM1 epitope, indicative of a posttranscriptional modification of IRF4 not seen in the normal counterpart.
Articolo in rivista - Articolo scientifico
Scientifica
B-Lymphocyte Subsets/chemistry/*immunology/*metabolism;Cell Movement/genetics/*immunology;DNA-Binding Proteins/*biosynthesis/deficiency/physiology;Flow Cytometry;Germinal Center/*cytology/*immunology/metabolism;Humans;Immunohistochemistry;Interferon Regulatory Factors/*biosynthesis/deficiency/physiology;Lymphoid Tissue/cytology/immunology/metabolism;Lymphoma, B-Cell/chemistry/immunology/pathology;Mice;Mice, Inbred C57BL;Mice, Knockout;Organ Specificity/genetics/immunology;Palatine Tonsil/cytology/immunology/metabolism;ranscription Factors/*biosynthesis/deficiency/physiology;Tumor Cells, Cultured
English
6930
6939
Cattoretti, G., Shaknovich, R., Smith, P., Jäck, H., Murty, V., & Alobeid, B. (2006). Stages of germinal center transit are defined by B cell transcription factor coexpression and relative abundance. JOURNAL OF IMMUNOLOGY, 117(10), 6930-6939.
Cattoretti, G; Shaknovich, R; Smith, P; Jäck, H; Murty, V; Alobeid, B
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/6502
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