| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Pathology, Columbia University Medical Center, New York, NY 10032;
Institute for Cancer Genetics, Columbia University, New York, NY 10032;
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10467; and
Division of Molecular Immunology, Department of Internal Medicine, Nikolaus-Fiebiger-Center, University of Erlangen-Nürnberg, Erlangen, Germany
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 Address correspondence and reprint requests to Dr. Giorgio Cattoretti at the current address: Department of Pathology, Azienda Ospedaliera San Gerardo, Via Pergolesi 33, 20052 Monza (MI), Italy. E-mail address: giocatto{at}gmail.com
2 Abbreviations used in this paper: TF, transcription factor; IRF, IFN regulatory factor; GC, germinal center; AID, activation-induced cytidine deaminase; BCL, B cell lymphoma; DLBCL, diffuse large BCL; IHC, immunohistochemistry; DAPI, 4',6'-diamidino-2-phenylindole; TMA, tissue microarray; FCM, flow cytometry; CLL, chronic lymphocytic leukemia; PRDM1, positive regulatory domain 1.
This article has been cited by other articles:
|
|
 |
|
  T. C. Kuo, A. L. Shaffer, J. Haddad Jr., Y. S. Choi, L. M. Staudt, and K. Calame Repression of BCL-6 is required for the formation of human memory B cells in vitro J. Exp. Med., April 16, 2007; 204(4): 819 - 830. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Natkunam The Biology of the Germinal Center Hematology, January 1, 2007; 2007(1): 210 - 215. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
