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 antigen CD72. So far, no functional evidence has been given for this interaction. We used soluble native CD5 and two anti-CD72 monoclonal antibodies, JT3 and WL225, produced and characterized in our laboratory in order to investigate the role of CD5 in B cell activation. Neither the CD5 nor the antibodies induced thymidine incorporation when added to resting human B cells, but they produced a two- to five-fold increase in thymidine uptake of B cells activated using immobilized anti-sIgM mAb when compared to the cultures stimulated by anti-sIgM mAb alone. The CD5 protein was effective at concentrations as low as 0.15 microM and its effect could be abolished by preincubation with soluble recombinant CD72 but not by preincubation with control proteins, indicating the specificity of the binding. The two antibodies but not the soluble CD5 produced a costimulatory effect when B cells were stimulated with suboptimal 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 physiologic humoral responses is discussed here.