B-CELL ACTIVATION BY HELPER T-CELL MEMBRANES

Resting B cells can be stimulated to proliferate and differentiate to antibody-producing cells by the combination of cell contact and solubl e signals provided by activated primed helper T (Th) cells. The abilit y of purified plasma membranes from activated Th cell clones and recom binant lymphokines to reconstitute B cell proliferation and differenti ation has allowed an increased understanding of B cell activation and characterization of the molecules involved. B cell-Th cell contact app ears sufficient for delivering the proliferative signal to B cells in the absence of lymphokines. A receptor ligand pair that plays a critic al role in delivery of the contact signal is CD40 on the B cell surfac e and the ligand for CD40 on activated Th cells. Lymphokines alone do not drive resting B cell differentiation; however, when these soluble signals are delivered during the time of B cell DNA replication, they effect B cell differentiation and isotype switching. Delivery of the C D40-dependent contact signal to resting B cells appears to require a h igh degree of CD40 crosslinking on the B cell surface. Providing conta ct signals to naive B cells with recombinant molecules in membrane fra ctions may allow the generation of methodology to support the producti on of novel antibodies in vitro.