Regulation of B-Cell Self-Tolerance By BAFF and the Molecular Basis of Its Action

摘要: Signals delivered following the binding of BAFF to its receptor BAFF-R are essential for survival mature conventional B cells. In order maintain self-tolerance, cells that express antigen receptors with significant reactivity against self-antigens prevented from receiving or responding these signals. The great majority produced bone marrow precursors fail join peripheral B-cell pool either due their self-reactivity a stochastic failure receive adequate signals limiting levels available in vivo. tight control over expression plays an important role enforcing as is illustrated by escape some self-reactive clones and production autoantibodies accompanies elevation Recent experiments have identified molecular basis unique dependence on BAFF. absence BAFF, constitutively suppressed through cooperative actions TRAF2 TRAF3 signal adapters. circumvents this activity triggering recruitment causing depletion cell via TRAF2-dependent mechanism. way, critical such alternative NF-κB pathway activated. Sustained exposure normally required pathways survival. However, requirement completely removed lack TRAF3.