Effects of CD40 stimulation in the prevention of human EBV-lymphomagenesis

CD40 is a molecule present on B lineage cells, both normal and neoplastic. Signalling through CD40 has been demonstrated to promote B cell growth and differentiation in vitro. In contrast to its effects on normal B cells, we have found that CD40 stimulation can inhibit the growth of various aggressive histology human B cell lymphomas both in vitro and in vivo. Moreover, using a human/mouse chimera model in which human EBV-induced B cell lymphomas can spontaneously arise, we have found that CD40 stimulation an prevent the occurrence of this human lymphoma in mice. However, normal human B cell engraftment and function was not adversely affected in these mice by CD40 stimulation. This indicates that CD40 stimulation is selective in its effects on aggressive histology B cell lymphomas. Thus, CD40 stimulation either by antibody or a recombinant soluble ligand, may be of potential clinical use, not only in the treatment of EBV-induced B cell lymphomas, but also in their prevention.