Pertussis toxin inhibition of anti-immunoglobulin-stimulated proliferation and inositol phosphate formation.
A variety of receptor agonists activate cells by stimulating polyphosphoinositide hydrolysis. Increasing evidence supports the concept that receptor-stimulated phosphoinositide hydrolysis is mediated by a guanosine triphosphate binding protein, which in some cell systems is inhibited by pertussis toxin through ADP-ribosylation. The cross-linking of membrane immunoglobulin by antigen or anti-Ig stimulates phosphoinositide hydrolysis resulting in the formation of inositol phosphate and diacylglycerol which act as second messengers in initiating B lymphocyte activation. In this report, we demonstrate that anti-Ig-stimulated inositol phosphate formation is enhanced by the nonhydrolyzable guanosine triphosphate analogue, GppNHp, in permeabilized B lymphocytes and also inhibited by pretreatment of intact cells with pertussis toxin. This latter effect is associated with the pertussis toxin-catalyzed ADP-ribosylation of a 41-kDa membrane protein which is of the same molecular weight as the guanosine triphosphate binding protein reported to mediate receptor-stimulated phosphoinositide hydrolysis in other cellular receptor systems. B lymphocyte proliferation induced by agents such as lipopolysaccharide and PMA plus calcium ionophore, which activate cellular proliferation without stimulating phosphoinositide breakdown, is not inhibited by pertussis toxin. We conclude that anti-Ig activation of B lymphocytes contains pertussis toxin- and guanosine triphosphate-sensitive components which are involved in regulating phosphoinositide breakdown and initiating cellular activation.
Blank
J A
JA
Immunotoxicology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Clark
G C
GC
Wiegand
G
G
Luster
M I
MI
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000378:metabolism / Q000502:physiology; D000242:Cyclic AMP / Q000097:blood; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology; D006160:Guanosine Triphosphate / Q000502:physiology; D007136:Immunoglobulins / Q000276:immunology*; D007295:Inositol Phosphates / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D037342:Pertussis Toxin; D013997:Time Factors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D000888:Antibodies, Anti-Idiotypic; D007136:Immunoglobulins; D007295:Inositol Phosphates; D010566:Virulence Factors, Bordetella; D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins