The Effect of Deleting p110{delta} on the Phenotype and Function of PTEN-Deficient B Cells

Janas, M. L., Hodson, D., Stamataki, Z., Hill, S., Welch, K., Gambardella, L., Trotman, L. C., Pandolfi, P. P., Vigorito, E., Turner, M. (January 2008) The Effect of Deleting p110{delta} on the Phenotype and Function of PTEN-Deficient B Cells. Journal of Immunology, 180 (2). pp. 739-46. ISSN 0022-1767

URL: http://www.ncbi.nlm.nih.gov/pubmed/18178811

Abstract

Control of the intracellular levels of phosphatidylinositol-(3, 4, 5)-trisphosphate by PI3K and phosphatase and tensin homolog (PTEN) is essential for B cell development and differentiation. Deletion of the PI3K catalytic subunit p110delta leads to a severe reduction in B1 and marginal zone (MZ) B cells, whereas deletion of PTEN results in their expansion. We have examined the relationship between these two molecules by generating mice with a B cell-specific deletion of PTEN (PTEN(B)) and a concurrent germline deletion of p110delta. The expanded B1 cell population of PTEN(B) mice was reduced to normal levels in PTEN(B)/p110delta mutant mice, indicating a critical role for the p110delta isoform in the expansion of B1 cells. However, numbers of MZ B cells in the PTEN(B)/p110delta mutants was intermediate between wild-type and PTEN(B)-deficient mice, suggesting an additional role for other PI3K catalytic isoforms in MZ differentiation. Furthermore, the defective class switch recombination in PTEN(B) B cells was only partially reversed in PTEN(B)/p110delta double mutant B cells. These results demonstrate an epistatic relationship between p110delta and PTEN. In addition, they also suggest that additional PI3K catalytic subunits contribute to B cell development and function.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > PTEN
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
CSHL Authors:
Communities: CSHL labs > Trotman lab
Depositing User: Brian Soldo
Date: 15 January 2008
Date Deposited: 23 Mar 2012 16:07
Last Modified: 08 May 2013 16:33
Related URLs:
URI: http://repository.cshl.edu/id/eprint/25520

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