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

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.

• 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)

Chemical References

• IGIP protein, human
• Immunoglobulin A
• Immunoglobulin D
• Proteins

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