p53 regulates Btk‐dependent B cell proliferation but not differentiation

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.