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Published online before print February 3, 2006

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(Journal of Leukocyte Biology. 2006;79:852-859.)
© 2006 by Society for Leukocyte Biology

p53 regulates Btk-dependent B cell proliferation but not differentiation

Nathan W. Schmidt^*, Lindsey D. Mayo, David B. Donner^* and Mark H. Kaplan^*,1

^* Departments of Pediatrics and Microbiology and Immunology and Walther Oncology Center, Indiana University School of Medicine, and Walther Cancer Institute, Indianapolis, Indiana; and
Departments of Radiation Oncology and Pharmacology, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio

¹Correspondence: Department of Pediatrics and Microbiology and Immunology, HB Wells Center for Pediatric Research, Indiana University School of Medicine, 702 Barnhill Dr., RI 2600, Room 302, Indianapolis, IN 46202. E-mail: mkaplan2{at}iupui.edu

Btk is critical for B cell development and proliferation. Mice lacking Btk have a defect in B cell development, resulting in a loss of mature B cells and decreased proliferative responses following B cell receptor cross-linking. In contrast, mice deficient in the tumor suppressor p53 display increases in developing B cell populations in the bone marrow. To investigate the potential role of p53 in Btk-dependent B cell development and function, we generated mice doubly-deficient in p53 and Btk. Btk/p53-deficient mice showed an increase in splenic B220+ cell numbers compared with Btk-deficient mice, although there was no recovery in B cell subset differentiation. In contrast to the lack of recovery of B cell development, there was a recovery in lipopolysaccharide and anti-immunoglobulin M (IgM) plus interleukin-4-induced proliferation of Btk/p53-deficient B cells, although there was no recovery to anti-IgM stimulation alone. Thus, p53 promotes B cell expansion and proliferation, but p53 deficiency cannot compensate for Btk deficiency in the development of B cell subsets.

Key Words: B lymphocyte • immunoglobulin • tumor suppressor • development

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