Induction of costimulatory molecule B7 in M12 B lymphomas by cAMP or MHC-restricted T cell interaction.
M12 B lymphomas expressing transfected Ak molecules with truncated cytoplasmic domains have a defect in Ag presentation to some autoreactive T cell hybrids. This defect in Ag presentation is corrected by pretreatment of the B cells with agents that elevate intracellular cAMP. Here we show that dibutyryl-cAMP treatment of M12 B lymphomas leads to cell surface expression of the costimulatory molecule B7. Furthermore, CTLA4Ig, a ligand for B7, inhibits activation of an accessory signal-dependent T hybrid. B7 is also inducible in M12 B lymphomas upon MHC-restricted interaction with T cells that can be activated by the APC, but not by T cells that fail to respond to truncated MHC-bearing M12 cells. Activation of the unresponsive T hybrids with immobilized anti-CD3 confers on them the ability to induce B7 in the APC. Direct engagement by immobilized antibodies of MHC class II on M12 B lymphomas did not induce B7 expression. Taken together, these results imply that during T-B interaction, initial T cell activation events lead to the ability of the T cell to induce costimulatory activity in the B cell, which in turn further activates the T cell. Activated T cell supernatants induced a small amount of B7 but were not nearly as effective as cAMP or as coincubation of T and B cells. These results suggest a role for T-B contact or localized cytokine secretion in the induction of B7 during T-B interaction.
Watts
T H
TH
Department of Immunology, University of Toronto, Ontario, Canada.
Alaverdi
N
N
Wade
W F
WF
Linsley
P S
PS
D000954:Antigens, Surface / Q000096:biosynthesis* / Q000276:immunology; D018122:B7-1 Antigen; D003994:Bucladesine / Q000494:pharmacology*; D002450:Cell Communication / Q000276:immunology*; D002460:Cell Line; D002474:Cell-Free System / Q000276:immunology; D002772:Cholera Toxin / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000954:Antigens, Surface; D018122:B7-1 Antigen; D000949:Histocompatibility Antigens Class II; D003994:Bucladesine; D002772:Cholera Toxin; D019204:GTP-Binding Proteins