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 mu-alpha switch circles from IgM(+) IgD(+) naive human B cells, indicating its role as an IgA switch factor.
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Authors | Mark A Endsley, Leo M Njongmeta, Elisabeth Shell, Matthew W Ryan, Alexander J Indrikovs, Seckin Ulualp, Randall M Goldblum, Waithaka Mwangi, D Mark Estes |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 182
Issue 4
Pg. 1854-9
(Feb 15 2009)
ISSN: 1550-6606 [Electronic] United States |
PMID | 19201837
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- IGIP protein, human
- Immunoglobulin A
- Immunoglobulin D
- Proteins
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Topics |
- B-Lymphocytes
(cytology, immunology)
- Cell Differentiation
(immunology)
- Dendritic Cells
(immunology, metabolism)
- Enzyme-Linked Immunosorbent Assay
- Gene Expression Regulation
(immunology)
- Humans
- Immunoglobulin A
(biosynthesis)
- Immunoglobulin Class Switching
(immunology)
- Immunoglobulin D
(immunology)
- Lymphocyte Activation
(immunology)
- Proteins
(immunology)
- Reverse Transcriptase Polymerase Chain Reaction
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