NATIVE SOLUBLE CD5 DELIVERS A COSTIMULATORY SIGNAL TO RESTING HUMAN B-LYMPHOCYTES

Recently, we reported that the CD5 protein can bind to the B cell anti gen CD72. So far, no functional evidence has been given for this inter action. We used soluble native CD5 and two anti-CD72 monoclonal antibo dies, JT3 and WL225, produced and characterized in our laboratory in o rder to investigate the role of CD5 in B cell activation. Neither the CD5 nor the antibodies induced thymidine incorporation when added to r esting human B cells, but they produced a two- to five-fold increase i n thymidine uptake of B cells activated using immobilized anti-sIgM mA b when compared to the cultures stimulated by anti-sIgM mAb alone. The CD5 protein was effective at concentrations as low as 0.15 mu M and i ts effect could be abolished by preincubation with soluble recombinant CD72 but not by preincubation with control proteins, indicating the s pecificity of the binding. The two antibodies but not the soluble CD5 produced a costimulatory effect when B cells were stimulated with subo ptimal concentrations of anti-CD40 mAb or IL-4. Altogether these data suggest that a costimulatory signal can be delivered to human B cells by CD5/CD72 interaction. The possible role of CD5/CD72 signalling in p hysiologic humoral responses is discussed here. (C) 1996 Academic Pres s, Inc.