Human IgA-inducing protein from dendritic cells induces IgA production by naive IgD+ B cells.
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.
Endsley
Mark A
MA
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA .
Njongmeta
Leo M
LM
Shell
Elisabeth
E
Ryan
Matthew W
MW
Indrikovs
Alexander J
AJ
Ulualp
Seckin
S
Goldblum
Randall M
RM
Mwangi
Waithaka
W
Estes
D Mark
DM
D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis*; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007072:Immunoglobulin D / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D011506:Proteins / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C538838:IGIP protein, human; D007070:Immunoglobulin A; D007072:Immunoglobulin D; D011506:Proteins