Imbalanced PTEN and PI3K Signaling Impairs Class Switch Recombination
Year: 2015
Type: article
Abstract: Class switch recombination (CSR) generates isotype-switched Abs with distinct effector functions. B cells express phosphatase and tensin homolog (PTEN) and multiple isoforms of class IA PI3K catalytic subunits, including p110α and p110δ, whose roles in CSR remain unknown or controversial. In this article, we demonstrate a direct effect of PTEN on CSR signaling by acute deletion of Pten specifically in mature B cells, thereby excluding the developmental impact of Pten deletion. We show that mature B cell-specific PTEN overexpression enhances CSR. More importantly, we establish a critical role for p110α in CSR. Furthermore, we identify a cooperative role for p110α and p110δ in suppressing CSR. Mechanistically, dysregulation of p110α or PTEN inversely affects activation-induced deaminase expression via modulating AKT activity. Thus, our study reveals that a signaling balance between PTEN and PI3K isoforms is essential to maintain normal CSR.
Source: The Journal of Immunology
Institutions: National Jewish Health, University of Colorado Anschutz
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: Antigen Recognition by Lymphocytes, G327943990, Infectious Agents and B Cell Anergy, Mechanisms promoting translocations and mature B cell lymphomas, G41015762, Role of Target DNA sequences in mutation and DNA Break Generation, Molecular Mechanisms of Immune Tolerance, Genomic instability mediated via differential DNA repair mechanisms in B cells
OpenAlex ID: W1827897568