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Published online before print February 3, 2006

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0705402

Received for publication July 21, 2005.
Revised November 29, 2005.
Accepted for publication December 6, 2005.

Article

p53 regulates Btk-dependent B cell proliferation but not differentiation

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

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

^@ To whom correspondence should be addressed. E-mail: mkaplan2{at}iupui.edu.

	Abstract

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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