The p85β regulatory subunit of phosphoinositide 3-kinase has unique and redundant functions in B cells

• Published in: Autoimmunity (Chur, Switzerland) Switzerland), 2009-01, Vol.42 (5), p.447-458
• Main Authors: Oak, Jean S., Chen, Jing, Peralta, Raechel Q., Deane, Jonathan A., Fruman, David A.
• Format: Article
• Language: English
• Subjects: B cells; cell activation; cell proliferation; lymphocyte development; signal transduction
• ISSN: 0891-6934; 1607-842X
• DOI: 10.1080/08916930902911746

Phosphoinositide kinase (PI3K) is activated by various receptors on lymphocytes and regulates development, activation, and tolerance. Genetic ablation of PI3K function in T cells leads to the appearance of autoimmune disorders. In B cells, loss of the class IA regulatory subunit p85α causes a partial defect in B cell development and proliferation, whereas loss of p85β alone causes no apparent changes in B cell function. Here we investigate further the consequences of p85β deletion in B cells, in the presence or absence of p85α. We demonstrate that p85β partially compensates for loss of p85α in B cell development and peripheral survival, with greater defects observed when both isoforms are absent. BCR-mediated AKT phosphorylation is partially reduced in p85α-deficient B cells and further diminished with concomitant loss of p85β. Unexpectedly, loss of p85β results in increased BCR-mediated proliferation and ERK phosphorylation. These results indicate that the p85β regulatory isoform has partially overlapping functions with p85α in B cells as well as a unique role in opposing BCR responses.