Correlation between ribosylation of pertussis toxin substrates and inhibition of peptidoglycan-, muramyl dipeptide- and lipopolysaccharide-induced mitogenic stimulation in B lymphocytes.
Selective inhibition by pertussis toxin (PT) of mitogenic activation of mouse B lymphocytes by bacterial mitogens (peptidoglycan and lipopolysaccharide) and muramyl dipeptide (a synthetic analog of peptidoglycan fragment) was demonstrated. Mitogenic activation of B cells by protein kinase C activators and ionomycin was insensitive to PT. Also PT did not inhibit peptidoglycan- and lipopolysaccharide-induced differentiation of B cells into Ig-secreting cells, when it was added to the cultures after the proliferative stage of the response. B lymphocyte membranes contained two major PT substrates (40 and 41 kDa). The extent of PT-mediated ADP ribosylation of these substrates correlated with the degree of PT-mediated inhibition of mitogenic stimulation of B cells. B cell stimulation by all mitogens tested was not inhibited by cholera toxin at nontoxic concentrations that are known to cause maximal increase in cAMP in B cells. Since the only known substrates for PT-mediated ADP ribosylation in mammalian cells are the alpha subunits of some G proteins, our data suggest that G proteins are present in B cell membranes and that they are involved in B cell activation induced by bacterial mitogens.
Dziarski
R
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Department of Microbiology and Immunology, Indiana University School of Medicine, Gary 46408.
D000119:Acetylmuramyl-Alanyl-Isoglutamine; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D005260:Female; D006131:Growth Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008213:Lymphocyte Activation / Q000187:drug effects*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens; D010457:Peptidoglycan; D037342:Pertussis Toxin; D010566:Virulence Factors, Bordetella / Q000378:metabolism / Q000494:pharmacology*
D006131:Growth Inhibitors; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D008934:Mitogens; D010457:Peptidoglycan; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D000246:Adenosine Diphosphate Ribose; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D003994:Bucladesine; D002772:Cholera Toxin; D037342:Pertussis Toxin