Human IgA-inducing protein from dendritic cells induces IgA production by naive IgD+ B cells

Mark A. Endsley, Leo M. Njongmeta, Elisabeth Shell, Matthew W. Ryan, Alexander J. Indrikovs, Seckin Ulualp, Randall M. Goldblum, Waithaka Mwangi, D. Mark Estes

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Over the last several years, there has been a great deal of progress in characterizing the role of dendritic cells (DCs) in the activation and modulation of B cells. DC-secreted chemokines can induce B cell trafficking to the lymph nodes. DC-produced survival factors such as B cell-activating factor of the TNF family and a proliferation-inducing ligand have been shown to be essential for B cell maturation, but have also been implicated in class-switch recombination and B cell lymphoma survival. Recently added to this list of DC-derived factors effecting B cells is IgA-inducing protein (IGIP). In this study, we characterize production of IGIP by human DCs, and examine its capacity to induce IgA class switching and differentiation of naive B cells in vitro. Monocyte-derived DCs were cultured in vitro with TLR agonists (TLR3, 4, 5, and 9) and other factors, including CD40 ligand, GM-CSF, and IL-4 as well as the neuropeptide vasoactive intestinal peptide. Under in vitro stimulation with vasoactive intestinal peptide and CD40L, IGIP mRNA expression could be up-regulated as much as 35-fold above nonstimulated samples within 12-48 h. Naive B cells cultured with exogenous recombinant human IGIP produced IgA in greater quantities than nonstimulated controls. Finally, we demonstrate that IGIP stimulation drives the production of μ-α switch circles from IgM+IgD+ naive human B cells, indicating its role as an IgA switch factor.

Original languageEnglish (US)
Pages (from-to)1854-1859
Number of pages6
JournalJournal of Immunology
Volume182
Issue number4
DOIs
StatePublished - Feb 15 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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