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Molecular and Cellular Biology, March 2001, p. 1531-1539, Vol. 21, No. 5
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.5.1531-1539.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

The B Lymphocyte-Specific Coactivator BOB.1/OBF.1 Is Required at Multiple Stages of B-Cell Development

Jochen Hess,1,2,dagger Peter J. Nielsen,3 Klaus-Dieter Fischer,1,2 Hermann Bujard,4 and Thomas Wirth1,2,*

Institut für Medizinische Strahlenkunde und Zellforschung (MSZ), Universität Würzburg, D-97078 Würzburg,1 Abteilung Physiologische Chemie, Universität Ulm, D-89081 Ulm,2 Max Planck Institut für Immunbiologie (MPI) D-79108 Freiburg,3 and Zentrum für Molekulare Biologie Heidelberg (ZMBH), D-69120 Heidelberg,4 Germany

Received 14 August 2000/Returned for modification 19 September 2000/Accepted 22 November 2000

The transcriptional coactivator BOB.1/OBF.1 confers B-cell specificity on the transcription factors Oct1 and Oct2 at octamer site-containing promoters. A hallmark of the BOB.1/OBF.1 mutation in the mouse is the absence of germinal center development in secondary lymphoid organs, demonstrating the requirement for BOB.1/OBF.1 in antigen-dependent stages of B-cell differentiation. Here we analyzed earlier stages of B lymphopoiesis in BOB.1/OBF.1-deficient mice. Examination of B-cell development in the bone marrow revealed that the numbers of transitional immature (B220+ IgMhi) B cells were reduced and that B-cell apoptosis was increased. When in competition with wild-type cells, BOB.1/OBF.1-/- bone marrow cells exhibited defects in repopulating the bone marrow B-cell compartment and were unable to establish a presence in the periphery of host mice. The defective bone marrow populations in BOB.1/OBF.1-/- mice were rescued by conditional expression of a BOB.1/OBF.1 transgene controlled by the tetracycline gene expression system. However, the restored populations did not restore the numbers of IgDhi B cells in the periphery, where the BOB.1/OBF.1 transgene was not expressed. These results show that BOB.1/OBF.1-/- B cells exhibit multistage defects in B-cell development, including impaired production of transitional B cells and defective maturation of recirculating B cells.

* Corresponding author. Mailing address: Abteilung Physiologische Chemie, Universität Ulm, Albert-Einstein-Allee 11, D-89081 Ulm, Germany. Phone: 49 (0) 731 502 3271. Fax: 49 (0) 731 502 2892. E-mail: thomas.wirth{at}medizin.uni-ulm.de.

dagger Present address: DKFZ, 69120 Heidelberg, Germany.

Molecular and Cellular Biology, March 2001, p. 1531-1539, Vol. 21, No. 5
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.5.1531-1539.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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