In Vivo GP39-CD40 Interactions Occur in the Non-Follicular Compartments of the Spleen and are Essential for Thymus Dependent Antibody Responses and Germinal Center Formation

The initiation of thymus-dependent (TD) antibody responses requires class ll-restricted antigen-specific helper T cell cognate interactions with B cells. None of the molecularly cloned cytokines, alone or in combination, can replace the contact-dependent requirement for B cell activation1. The molecule which mediates the contact-dependent signal is a 39 kD membrane protein which is expressed on the surface of activated T-helper (Th) cells2,3. This membrane protein, gp39, was identified as the ligand for the B cell membrane protein CD40. CD40, a mitogenic receptor expressed on all mature B lymphocytes4, is a type I membrane protein and member of the TNF receptor family5. Evidence that CD40 is an important receptor on B cells is derived from studies that anti-CD40 mAb and cofactors such as anti-immunoglobulin (Ig) and cytokines initiate both B cell growth and differentiation6,7.