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 language | English (US) |
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Pages (from-to) | 1789-1798 |
Number of pages | 10 |
Journal | International Immunology |
Volume | 16 |
Issue number | 12 |
DOIs | |
State | Published - Dec 1 2004 |
Externally published | Yes |
Keywords
- B lymphocytes
- Cellular differentiation
- Signal transduction
- Spleen
- Transgenic/knockout
ASJC Scopus subject areas
- Immunology