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p53 regulates Btk‐dependent B cell proliferation but not differentiation
Author(s) -
Schmidt Nathan W.,
Mayo Lindsey D.,
Donner David B.,
Kaplan Mark H.
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0705402
Subject(s) - bruton's tyrosine kinase , b cell , biology , cell growth , microbiology and biotechnology , cell , cancer research , immunology , antibody , signal transduction , tyrosine kinase , biochemistry
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.