B cell-intrinsic and -extrinsic regulation of antibody responses by PARP14, an intracellular (ADP-Ribosyl)transferase

Sung Hoon Cho, Ariel Raybuck, Mei Wei, John Erickson, Ki Taek Nam, Reagan G. Cox, Alyssa Trochtenberg, James W. Thomas, John Williams, Mark Boothby

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17 Citations (Scopus)

Abstract

The capacity to achieve sufficient concentrations of Ag-specific Ab of the appropriate isotypes is a critical component of immunity that requires efficient differentiation and interactions of Ag-specific B and Th cells along with dendritic cells. Numerous bacterial toxins catalyze mono(ADP-ribosyl)ation of mammalian proteins to influence cell physiology and adaptive immunity. However, little is known about biological functions of intracellular mammalian mono(ADP-ribosyl)transferases, such as any ability to regulate Ab responses. poly-(ADP-ribose) polymerase 14 (PARP14), an intracellular protein highly expressed in lymphoid cells, binds to STAT6 and encodes a catalytic domain with mammalian mono(ADP-ribosyl)transferase activity. In this article, we show that recall IgA as well as the STAT6-dependent IgE Ab responses are impaired in PARP14-deficient mice. Whereas PARP14 regulation of IgE involved a B cell-intrinsic process, the predominant impact on IgA was B cell extrinsic. Of note, PARP14 deficiency reduced the levels of Th17 cells and CD103+ DCs, which are implicated in IgA regulation. PARP14 enhanced the expression of RORa, Runx1, and Smad3 after T cell activation, and, importantly, its catalytic activity of PARP14 promoted Th17 differentiation. Collectively, the findings show that PARP14 influences the class distribution, affinity repertoire, and recall capacity of Ab responses in mice, as well as provide direct evidence of the requirement for protein mono-ADP-ribosylation in Th cell differentiation.

Original languageEnglish
Pages (from-to)3169-3178
Number of pages10
JournalJournal of Immunology
Volume191
Issue number6
DOIs
Publication statusPublished - 2013 Sep 15

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Cho, S. H., Raybuck, A., Wei, M., Erickson, J., Nam, K. T., Cox, R. G., Trochtenberg, A., Thomas, J. W., Williams, J., & Boothby, M. (2013). B cell-intrinsic and -extrinsic regulation of antibody responses by PARP14, an intracellular (ADP-Ribosyl)transferase. Journal of Immunology, 191(6), 3169-3178. https://doi.org/10.4049/jimmunol.1301106