ABSTRACT
Protein kinase A (PKA) is a holoenzyme composed of a regulatory subunit dimer and two catalytic subunits and regulates numerous cellular functions including immune cell activity. There are two major catalytic subunit genes, PRKACA and PRKACB encoding the catalytic subunits Cα and Cß. The PRKACB gene encodes several splice variants including Cß2, which is enriched in T-, B- and natural killer cells. Cß2 is significantly larger (46 kDa) than any other C splice variant. In this study we characterized mice ablated for the Cß2 protein demonstrating a significantly reduced cAMP-induced catalytic activity of PKA in the spleenocytes, lymphocytes and thymocytes. We also observed a significantly increased number of CD62L-expressing CD4+ and CD8+ T cells in LNs, accompanied by increased susceptibility to systemic inflammation by the Cß2 ablated mice. The latter was reflected in an elevated sensitivity to collagen-induced arthritis (CIA), as well as higher concentration of TNF-α and lower concentration of IL-10 in response to LPS challenges. We suggest a role of Cß2 in regulating innate as well as adaptive immune sensitivity in vivo.