In view of the fact that CD40 signals proliferation of non-transformed B-cells [114] and protects B-cells from cell surface immunoglobulin- and CD95-induced cell death [115,116,117], the cytotoxic activity of anti-CD40 antibodies on B-cell lymphomas is at first glance counterintuitive but could reflect that the cellular vulnerability to CD40 depends from signal strength, context and differentiation status of the cell. This evidence concerns the gene CD40 and B-cell non-Hodgkin lymphoma.