Modulation of B-cell activation by the B subunit of Escherichia coli enterotoxin: receptor interaction up-regulates MHC class II, B7, CD40, CD25 and ICAM-1.
The B subunits of cholera toxin (CtxB) and Escherichia coli heat-labile enterotoxin (EtxB) are non-toxic lectins that bind and cross-link a ubiquitous cell glycolipid receptor, ganglioside GM1, and are recognized as potent mucosal and systemic immunogens. Here we examine the role of EtxB receptor occupancy in modulating the activation of B cells, in vitro, in primary lymphocyte cultures containing B and T cells. When 48-hr spleen cell cultures containing EtxB were compared with those in the presence of a non-receptor binding mutant, EtxB(G33D), a marked shift in the ratio of CD4+ T cells: B cells was noted. Evidence suggested that this was the result of either enhanced survival or proliferation of B cells associated with receptor occupancy by EtxB. Investigation revealed that EtxB induced only a minimal increase in proliferation above that of EtxB(G33D), in mixed cell cultures, and failed to induce any cell division of purified B cells or T cells. In contrast, receptor-binding by EtxB markedly up-regulated the expression of major histocompatability complex (MHC) class II, B7, intracellular adhesion molecule-1 (ICAM-1), CD40 and CD25 on the B-cell surface. These results indicate that the polyclonal effects of EtxB on B cells are not associated with wide-scale proliferation, but more likely with maintenance of B-cell survival by activation of molecules essential for B-cell differentiation. The findings also highlight the essential role of GM1-interaction with EtxB in the regulation of lymphocyte responses.
Nashar
T O
TO
School of Medical Sciences, University of Bristol, UK.
Hirst
T R
TR
Williams
N A
NA
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D018122:B7-1 Antigen / Q000378:metabolism; D001427:Bacterial Toxins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000378:metabolism; D018929:Cell Culture Techniques; D002455:Cell Division / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology*; D029968:Escherichia coli Proteins; D005260:Female; D006162:Guanylate Cyclase / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D018000:Receptors, Peptide / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
D018122:B7-1 Antigen; D001427:Bacterial Toxins; D019013:CD40 Antigens; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D000949:Histocompatibility Antigens Class II; D015375:Receptors, Interleukin-2; D018000:Receptors, Peptide; D018799:Intercellular Adhesion Molecule-1; C027538:heat-labile enterotoxin, E coli; D006162:Guanylate Cyclase; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled