title: Effects of cholera toxin on human B cells. Cholera toxin induces B cell surface DR expression while it inhibits anti-mu antibody-induced cell proliferation.
abstract: Experiments were performed to investigate the effect of cholera toxin (CT) on human B cell function. Highly purified (greater than 98% CD20+) human peripheral blood B cells were exposed to CT in the presence or absence of anti-mu antibody. Treatment of highly purified B cells with CT stimulated enhanced expression of surface DR molecules, whereas it did not enhance expression of other B cell surface activation markers including transferrin or IL-2R. Neither the A nor the B subunits of CT by themselves enhanced the expression of surface DR Ag. In addition, 8-bromo-cAMP alone or in combination with the B subunit did not increase the expression of human B cell surface DR Ag. These findings suggest that neither elevation of cAMP nor binding to GM1 ganglioside are sufficient to stimulate this activation parameter in B cells. Associated with CT-mediated enhanced expression of MHC class II molecules we found that CT-treated B cells also served as stronger stimulators, compared with control cells, of both autologous and allogeneic MLR responses in peripheral blood T cells. Although CT stimulated early events in B cell activation, it inhibited anti-mu antibody-induced B cell thymidine incorporation by 55 to 75%. Inhibitory effects of CT were observed even when CT was added to cultures as late as 36 h after the addition of the anti-mu antibody. These results suggest that CT has both a stimulatory and inhibitory effect on human B cells and that the stimulatory effect may be mediated via a cAMP-independent mechanism.
authors.affiliation: Kidney Diseases Section, National Institute of Diabetes Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD 20892.
authors.forename: E D
authors.initials: ED
authors.lastname: Anastassiou
authors.forename: H
authors.initials: H
authors.lastname: Yamada
authors.forename: M L
authors.initials: ML
authors.lastname: Francis
authors.forename: J J
authors.initials: JJ
authors.lastname: Mond
authors.forename: G C
authors.initials: GC
authors.lastname: Tsokos
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D007148:Immunoglobulin mu-Chains / Q000276:immunology; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism*; D013997:Time Factors
chemical_list: D006684:HLA-DR Antigens; D007148:Immunoglobulin mu-Chains; D011947:Receptors, Antigen, B-Cell; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D002772:Cholera Toxin; D002118:Calcium