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Molecular and Cellular Biology, March 2001, p. 1531-1539, Vol. 21, No. 5
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
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

/
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.
Present address: DKFZ, 69120 Heidelberg, Germany.
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