Altered splenic B cell subset development in mice lacking phosphoinositide 3-kinase p85α

Amber C. Donahue, Kristen L. Hess, Kwan Ng, David A. Fruman

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The signaling enzyme phosphoinositide 3-kinase (PI3K) is activated following B cell receptor (BCR) engagement and by many other receptors on B lymphocytes. Mice lacking p85α, the predominant PI3K regulatory isoform, exhibit defects in B cell development and activation that are grossly similar to those found in mice lacking Bruton's tyrosine kinase (Btk) and other critical signaling molecules. However, a detailed analysis of splenic B cell subsets in p85α-deficient mice has not been reported. Here we show that these mice are deficient in four major B cell subsets: transitional-1, transitional-2, follicular and marginal zone. These defects are distinct from those observed in Xid mice that express a mutant Btk unable to interact with PI3K lipid products. Moreover, mice with both genetic lesions exhibit even greater impairment in B cell development. Finally, we show that transgenic expression of the anti-apoptotic protein Bcl-2 in p85α-deficient mice restores the transitional B cell subsets but not the marginal zone subset, and produces a follicular population with an aberrant phenotype. These findings establish a role for PI3K-p85α in differentiation of both follicular and marginal zone B cells, and suggest that these functions are required not solely for the propagation of anti-apoptotic signals.

Original languageEnglish (US)
Pages (from-to)1789-1798
Number of pages10
JournalInternational Immunology
Volume16
Issue number12
DOIs
StatePublished - Dec 1 2004
Externally publishedYes

Fingerprint

B-Lymphocyte Subsets
1-Phosphatidylinositol 4-Kinase
B-Lymphocytes
Apoptosis Regulatory Proteins
B-Lymphoid Precursor Cells
Protein Isoforms
Phenotype
Lipids
Enzymes
Population

Keywords

  • B lymphocytes
  • Cellular differentiation
  • Signal transduction
  • Spleen
  • Transgenic/knockout

ASJC Scopus subject areas

  • Immunology

Cite this

Altered splenic B cell subset development in mice lacking phosphoinositide 3-kinase p85α. / Donahue, Amber C.; Hess, Kristen L.; Ng, Kwan; Fruman, David A.

In: International Immunology, Vol. 16, No. 12, 01.12.2004, p. 1789-1798.

Research output: Contribution to journalArticle

Donahue, Amber C. ; Hess, Kristen L. ; Ng, Kwan ; Fruman, David A. / Altered splenic B cell subset development in mice lacking phosphoinositide 3-kinase p85α. In: International Immunology. 2004 ; Vol. 16, No. 12. pp. 1789-1798.
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