This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Greiner, A. Articles by Wirth, T. Search for Related Content PubMed PubMed Citation Articles by Greiner, A. Articles by Wirth, T.

(American Journal of Pathology. 2000;156:501-507.)
© 2000 American Society for Investigative Pathology

Regular Articles

Up-Regulation of BOB.1/OBF.1 Expression in Normal Germinal Center B Cells and Germinal Center-Derived Lymphomas

Axel Greiner^*, Kerstin B. Müller, Jochen Hess, Klaus Pfeffer, H. Konrad Müller-Hermelink^* and Thomas Wirth

From the Pathologisches Institut,^*
Würzburg; the Institut für Medizinische Strahlenkunde und Zellforschung,
Würzburg; and the Institut für Medizinische Mikrobiologie,
München, Germany

The BOB.1/OBF.1/OCAB.1 protein is a lymphocyte-specific transcriptional coactivator. It interacts with the Oct1 and Oct2 transcription factors and contributes to the transcriptional activity of octamer motifs. The analysis of established B cell lines had suggested that BOB.1/OBF.1 is constitutively expressed at all stages of B cell development. Here we show that expression of BOB.1/OBF.1 is regulated within the B cell lineage. Specifically, germinal center B cells show highly increased BOB.1/OBF.1 levels. We can induce the up-regulation by stimulating primary splenic B cells, eg, by triggering CD40 signaling in the presence of interleukin-4. Expression of BOB.1/OBF.1 is detectable but reduced in spleens from mice unable to undergo the germinal center reaction due to mutations in the TNF receptor p55 or lymphotoxin ß (LTß) receptor genes. Furthermore, we demonstrate that BOB.1/OBF.1 expression is highly regulated in human B cell lymphomas. Whereas lymphomas representing pre- and postfollicular B cell developmental stages are negative for BOB.1/OBF.1, high-level expression of BOB.1/OBF.1 is characteristic of germinal center-derived tumors. In these tumors BOB.1/OBF.1 is typically coexpressed with high levels of Bcl6. These results imply that overexpression of BOB.1/OBF.1, like overexpression of Bcl6, might play a role in the pathogenesis of germinal center-derived B cell lymphomas. Furthermore, overexpression of BOB.1/OBF.1 represents a characteristic feature of these tumors that is useful in their identification.

This article has been cited by other articles:

				B. Bartholdy, C. Du Roure, A. Bordon, D. Emslie, L. M. Corcoran, and P. Matthias The Ets factor Spi-B is a direct critical target of the coactivator OBF-1 PNAS, August 1, 2006; 103(31): 11665 - 11670. [Abstract] [Full Text] [PDF]

				C. Brunner and T. Wirth Btk expression is controlled by Oct and BOB.1/OBF.1. Nucleic Acids Res., January 1, 2006; 34(6): 1807 - 1815. [Abstract] [Full Text] [PDF]

				S. E. Coupland, C. Loddenkemper, J. R. Smith, R. M. Braziel, F. Charlotte, I. Anagnostopoulos, and H. Stein Expression of Immunoglobulin Transcription Factors in Primary Intraocular Lymphoma and Primary Central Nervous System Lymphoma Invest. Ophthalmol. Vis. Sci., November 1, 2005; 46(11): 3957 - 3964. [Abstract] [Full Text] [PDF]

				H. Laumen, C. Brunner, A. Greiner, and T. Wirth Myosin light chain 1 atrial isoform (MLC1A) is expressed in pre-B cells under control of the BOB.1/OBF.1 coactivator Nucleic Acids Res., March 5, 2004; 32(4): 1577 - 1583. [Abstract] [Full Text] [PDF]

				M. A. Sepulveda, A. V. Emelyanov, and B. K. Birshtein NF-{kappa}B and Oct-2 Synergize to Activate the Human 3' Igh hs4 Enhancer in B Cells J. Immunol., January 15, 2004; 172(2): 1054 - 1064. [Abstract] [Full Text] [PDF]

				C. Brunner, H. Laumen, P. J. Nielsen, N. Kraut, and T. Wirth Expression of the Aldehyde Dehydrogenase 2-like Gene Is Controlled by BOB.1/OBF.1 in B Lymphocytes J. Biol. Chem., November 14, 2003; 278(46): 45231 - 45239. [Abstract] [Full Text] [PDF]

				M. Jankovic and M. C. Nussenzweig OcaB regulates transitional B cell selection Int. Immunol., September 1, 2003; 15(9): 1099 - 1104. [Abstract] [Full Text] [PDF]

				C. Brunner, D. Marinkovic, J. Klein, T. Samardzic, L. Nitschke, and T. Wirth B Cell-specific Transgenic Expression of Bcl2 Rescues Early B Lymphopoiesis but Not B Cell Responses in BOB.1/OBF.1-deficient Mice J. Exp. Med., May 5, 2003; 197(9): 1205 - 1211. [Abstract] [Full Text] [PDF]

				J. Sun, G. Matthias, M. J. Mihatsch, K. Georgopoulos, and P. Matthias Lack of the Transcriptional Coactivator OBF-1 Prevents the Development of Systemic Lupus Erythematosus-Like Phenotypes in Aiolos Mutant Mice J. Immunol., February 15, 2003; 170(4): 1699 - 1706. [Abstract] [Full Text] [PDF]

				T. Samardzic, D. Marinkovic, P. J. Nielsen, L. Nitschke, and T. Wirth BOB.1/OBF.1 Deficiency Affects Marginal-Zone B-Cell Compartment Mol. Cell. Biol., December 1, 2002; 22(23): 8320 - 8331. [Abstract] [Full Text] [PDF]

				J. Hess, P. J. Nielsen, K.-D. Fischer, H. Bujard, and T. Wirth The B Lymphocyte-Specific Coactivator BOB.1/OBF.1 Is Required at Multiple Stages of B-Cell Development Mol. Cell. Biol., March 1, 2001; 21(5): 1531 - 1539. [Abstract] [Full Text]

				D. Re, M. Müschen, T. Ahmadi, C. Wickenhauser, A. Staratschek-Jox, U. Holtick, V. Diehl, and J. Wolf Oct-2 and Bob-1 Deficiency in Hodgkin and Reed Sternberg Cells Cancer Res., March 1, 2001; 61(5): 2080 - 2084. [Abstract] [Full Text]