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) |
|---|---|
| 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 |
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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 journal › Article
}
TY - JOUR
T1 - Altered splenic B cell subset development in mice lacking phosphoinositide 3-kinase p85α
AU - Donahue, Amber C.
AU - Hess, Kristen L.
AU - Ng, Kwan
AU - Fruman, David A.
PY - 2004/12/1
Y1 - 2004/12/1
N2 - 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.
AB - 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.
KW - B lymphocytes
KW - Cellular differentiation
KW - Signal transduction
KW - Spleen
KW - Transgenic/knockout
UR - http://www.scopus.com/inward/record.url?scp=10844255780&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=10844255780&partnerID=8YFLogxK
U2 - 10.1093/intimm/dxh180
DO - 10.1093/intimm/dxh180
M3 - Article
C2 - 15520044
AN - SCOPUS:10844255780
VL - 16
SP - 1789
EP - 1798
JO - International Immunology
JF - International Immunology
SN - 0953-8178
IS - 12
ER -