| First Author | Donahue AC | Year | 2004 |
| Journal | Int Immunol | Volume | 16 |
| Issue | 12 | Pages | 1789-98 |
| PubMed ID | 15520044 | Mgi Jnum | J:94022 |
| Mgi Id | MGI:3510527 | Doi | 10.1093/intimm/dxh180 |
| Citation | Donahue AC, et al. (2004) Altered splenic B cell subset development in mice lacking phosphoinositide 3-kinase p85{alpha}. Int Immunol 16(12):1789-1798 |
| abstractText | 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 p85alpha, 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 p85alpha-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 p85alpha-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-p85alpha 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. |
