Identification of soluble N-ethylmaleimide-sensitive factor attachment protein receptor exocytotic machinery in human plasma cells: SNAP-23 is essential for antibody secretion.
Plasma cells (PC) are B-lymphocytes terminally differentiated in a postmitotic state, with the unique purpose of manufacturing and exporting Igs. Despite the importance of this process in the survival of vertebrates, no studies have been made to understand the molecular events that regulate Ig exocytosis by PC. The present study explores the possible presence of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) system in human PC, and examines its functional role in Ig secretion. Syntaxin-2, Syntaxin-3, Syntaxin-4, vesicle-associated membrane protein (VAMP)-2, VAMP-3, and synaptosome-associated protein (SNAP)-23 could be readily detected in normal human PC obtained from intestinal lamina propria and blood, as well as in human PC lines. Because SNAP-23 plays a central role in SNAREs complex formation, it was chosen to examine possible functional implications of the SNARE system in PC Ig secretion. When recombinant SNAP-23 fusion protein was introduced into the cells, a complete abolishment of Ig production was observed in the culture supernatants of PC lines, as well as in those of normal PC. These results provide insights, for the first time, into the molecular machinery of constitutive vesicular trafficking in human PC Ig secretion and present evidence indicating that at least SNAP-23 is essential for Ab production.
Reales
Elena
E
Unidad de Investigación, Hospital Universitario Puerta del Mar, Cádiz, Spain.
Mora-López
Francisco
F
Rivas
Verónica
V
García-Poley
Antonio
A
Brieva
José A
JA
Campos-Caro
Antonio
A
D000917:Antibody Formation; D001483:Base Sequence; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D005089:Exocytosis / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism*; D050766:Qb-SNARE Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D050767:Qc-SNARE Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology; D050600:SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D018076:DNA, Complementary; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C100493:SNAP23 protein, human; D050600:SNARE Proteins