Syntaxin-4 is essential for IgE secretion by plasma cells.
The humoral immune system provides a crucial first defense against the invasion of microbial pathogens via the secretion of antigen specific immunoglobulins (Ig). The secretion of Ig is carried out by terminally differentiated B-lymphocytes called plasma cells. Despite the key role of plasma cells in the immune response, the mechanisms by which they constitutively traffic large volumes of Ig out of the cell is poorly understood. The involvement of Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins in the regulation of protein trafficking from cells has been well documented. Syntaxin-4, a member of the Qa SNARE syntaxin family has been implicated in fusion events at the plasma membrane in a number of cells in the immune system. In this work we show that knock-down of syntaxin-4 in the multiple myeloma U266 human plasma cell line results in a loss of IgE secretion and accumulation of IgE within the cells. Furthermore, we show that IgE co-localises with syntaxin-4 in U266 plasma cells suggesting direct involvement in secretion at the plasma membrane. This study demonstrates that syntaxin-4 plays a critical role in the secretion of IgE from plasma cells and sheds some light on the mechanisms by which these cells constitutively traffic vesicles to the surface for secretion. An understanding of this machinery may be beneficial in identifying potential therapeutic targets in multiple myeloma and autoimmune disease where over-production of Ig leads to severe pathology in patients.
Immunomodulation Group, School of Biotechnology, Dublin City University, Ireland.
Arman
A
Rahman
Joseph
J
Decourcey
Nadia Ben
NB
Larbi
Sinéad T
ST
Loughran
Dermot
D
Walls
Christine E
CE
Loscher
D045744:Cell Line, Tumor; D006801:Humans; D007073:Immunoglobulin E / Q000032:analysis / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism*; D010950:Plasma Cells / Q000378:metabolism*; D021381:Protein Transport; D050765:Qa-SNARE Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D051040:Vesicle-Associated Membrane Protein 3 / Q000235:genetics / Q000378:metabolism
D015850:Interleukin-6; D050765:Qa-SNARE Proteins; D051040:Vesicle-Associated Membrane Protein 3; D007073:Immunoglobulin E
FBS; Ig; IgE secretion; Multiple myeloma; PBS; Plasma cells; SNARE; Syntaxin-4; TNF; VAMP; VAMP3; fetal bovine serum; immunoglobulin; phosphate buffered saline; siRNA; small interfering RNA; soluble N-ethylmaleimide-sensitive factor attachment protein receptor; tumour necrosis factor; vesicle-associate membrane protein