Immunological memory, including both persistent and recall antibody (Ab) responses, enables more efficient and effective protection against infection, but key molecular mechanisms regulating emergence and persistence of memory B cells and plasma cells remain unclear. Poly-ADP-Ribose Polymerase14 (PARP14) is highly expressed in B cells and identified as a Stat6-interacting protein with intrinsic mono-ADP-ribosyltransferase (mART) activity. Although there are 17 PARP family members, the physiological function of most PARPs are not known well. Here we show that recall IgA and IgE production are impaired in PARP14-deficient mice. Further analysis revealed that, although PARP14 regulation of IgE involves B cell intrinsic function, IgA regulation by PARP14 was predominantly B cell extrinsic. Of note, PARP14 regulates the levels of CD103+ dendritic cells and T helper 17 (Th17) cells which might influence IgA generation in B cells. Moreover, PARP14 regulates the expression of RORα, Runx1 and Smad3 during Th17 differentiation, and mART activity of PARP plays a critical role in Th17 differentiation. Collectively, these results shed new light on differential mechanisms of Ig regulation, provide evidence that an endogenous mono ADP-ribosyltransferase regulates recall Ab production, and may have important implications for a new therapeutic target.
- Copyright © 2013 by The American Association of Immunologists, Inc.