Recent studies have identified CD40 ligand (CD40L) as the critical membrane-expressed molecule responsible for T cell dependent B-cell activation. CD40L co-operates with various cytokines to induce B-cell activation, proliferation, and immunoglobulin isotype switching. Some antigens, however, can also stimulate B-cell activation and isotype switching in the absence of CD40L or T cells. Recent studies have suggested that cytokines derived from non-T cells, such as natural killer cells, macrophages and mast cells, are responsible for isotype switching in T cell independent responses.