The Journal of Experimental Medicine
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Published 5 May 2003. doi:10.1084/jem.20022014
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© Rockefeller University Press, 0022-1007/2003/5/1205 $5.00
The Journal of Experimental Medicine, Volume 197, Number 9, 1205-1211


Brief Definitive Report

B Cell–specific Transgenic Expression of Bcl2 Rescues Early B Lymphopoiesis but Not B Cell Responses in BOB.1/OBF.1-deficient Mice

Cornelia Brunner1, Dragan Marinkovic1, Jörg Klein2, Tatjana Samardzic1, Lars Nitschke2 and Thomas Wirth1

1 Department of Physiological Chemistry, University of Ulm, D-89081 Ulm, Germany
2 Institute of Virology and Immunobiology, University of Wuerzburg, D-97078 Wuerzburg, Germany

Address correspondence to Thomas Wirth, Dept. of Physiological Chemistry, Albert-Einstein-Allee 11, University of Ulm, Ulm, D-89081 Germany. Phone: 49-73-15-02-3270; Fax: 49-73-15-02-2892; E-mail: thomas.wirth{at}medizin.uni-ulm.de

Mice deficient for the transcriptional coactivator BOB.1/OBF.1 show several defects in B cell differentiation. Numbers of immature transitional B cells in the bone marrow are reduced and fewer B cells reach the periphery. Furthermore, germinal center B cells are absent and marginal zone (MZ) B lymphocytes are markedly reduced. Increased levels of B cell apoptosis in these mice prompted us to analyze expression and function of antiapoptotic proteins. Bcl2 expression is strongly reduced in BOB.1/OBF.1-deficient pre–B cells. When BOB.1/OBF.1-deficient mice were crossed with Bcl2-transgenic mice, B cell development in the bone marrow and numbers of B cells in peripheral lymphoid organs were normalized. However, neither germinal center B cells nor MZ B cells were rescued. Additionally, Bcl2 did not rescue the defects in signaling and affinity maturation found in BOB.1/OBF.1-deficient mice. Interestingly, Bcl2-transgenic mice by themselves show an MZ B cell defect. Virtually no functional MZ B cells were detected in these mice. In contrast, mice deficient for Bcl2 show a relative increase in MZ B cell numbers, indicating a previously undetected function of Bcl2 for this B cell compartment.

Key Words: B cell differentiation • germinal center reaction • affinity maturation • marginal zone • transcription factor


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