p53 regulates Btk-dependent B cell proliferation but not differentiation

Nathan W. Schmidt, Lindsey Mayo, David B. Donner, Mark Kaplan

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)852-859
Number of pages8
JournalJournal of Leukocyte Biology
Volume79
Issue number4
DOIs
StatePublished - Apr 2006

Fingerprint

B-Lymphocytes
Cell Proliferation
B-Lymphocyte Subsets
Immunoglobulin M
Interleukin-4
Lipopolysaccharides
Cell Differentiation
Cell Count
Bone Marrow
Population
Neoplasms

Keywords

  • B lymphocyte
  • Development
  • Immunoglobulin
  • Tumor suppressor

ASJC Scopus subject areas

  • Cell Biology

Cite this

p53 regulates Btk-dependent B cell proliferation but not differentiation. / Schmidt, Nathan W.; Mayo, Lindsey; Donner, David B.; Kaplan, Mark.

In: Journal of Leukocyte Biology, Vol. 79, No. 4, 04.2006, p. 852-859.

Research output: Contribution to journalArticle

@article{421ad38de046472087f5ebeee5bb1a35,
title = "p53 regulates Btk-dependent B cell proliferation but not differentiation",
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.",
keywords = "B lymphocyte, Development, Immunoglobulin, Tumor suppressor",
author = "Schmidt, {Nathan W.} and Lindsey Mayo and Donner, {David B.} and Mark Kaplan",
year = "2006",
month = "4",
doi = "10.1189/jlb.0705402",
language = "English",
volume = "79",
pages = "852--859",
journal = "Journal of Leukocyte Biology",
issn = "0741-5400",
publisher = "FASEB",
number = "4",

}

TY - JOUR

T1 - p53 regulates Btk-dependent B cell proliferation but not differentiation

AU - Schmidt, Nathan W.

AU - Mayo, Lindsey

AU - Donner, David B.

AU - Kaplan, Mark

PY - 2006/4

Y1 - 2006/4

N2 - 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.

AB - 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.

KW - B lymphocyte

KW - Development

KW - Immunoglobulin

KW - Tumor suppressor

UR - http://www.scopus.com/inward/record.url?scp=33746425865&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33746425865&partnerID=8YFLogxK

U2 - 10.1189/jlb.0705402

DO - 10.1189/jlb.0705402

M3 - Article

VL - 79

SP - 852

EP - 859

JO - Journal of Leukocyte Biology

JF - Journal of Leukocyte Biology

SN - 0741-5400

IS - 4

ER -