CD40 belongs to the TNF receptor superfamily. While the biological role of some of the ligand-receptor pairs in this family still remains obscure, CD40 has proven its importance. A key role of CD40/CD40 ligand interactions in immune activation, particularly in T-cell dependent B cell responses is anticipated. This molecule as well as the other ligands of the family share the property of co-stimulation of T-cell proliferation and are all expressed by activated T-cells. The programmed cell death has been suggested to be involved in clonal elimination of self-reactive lymphocytes for the normal function of the immune system. Interaction with membrane bound self antigens may eliminate self-reactive nature B cells by apoptosis. Antigen-receptor mediated B cell apoptosis is blocked when a signal is transduced via the CD40 molecule on the B cell surface. Because the ligand of CD40 (CD40L) is expressed on activated T helper cells, B cells may escape from apoptosis and are activated when the immune system interacts with foreign antigens, which are normally able to activate T-helper cells. Thus the CD40 – CD40L interaction plays a central role in the various phases of the B cell response to T-dependent antigens. Taken together, B cells can participate in regulating their own destruction. Protection against Fas-dependent apoptosis afforded by immunoglobulin-receptor engagement may constitute a fail-safe mechanism that eliminates bystander B cells activated by CD40L – expressing T cells, but ensures survival of antigen-specific B cells. CD40 Ligand is expressed on the surface of activated CD4+ T cells, basophils, and mast cells. Binding of CD40L to its receptor, CD40, on the surface of B cells stimulates B-cell proliferation, adhesion and differentiation. A soluble isoform of CD40L has been shown to exist in the circulation. This soluble molecule is a homotrimer of a 18kDa protein exhibiting full activity in B cell proliferation and differentiation assays, is able to rescue B cells from apoptosis and binds soluble CD40.