The role of the BAFF/APRIL system in B cell homeostasis and lymphoid cancers

Current Opinion in Pharmacology
Fabienne Mackay, Stuart G Tangye

Abstract

Signaling through the B cell antigen receptor promotes activation and survival of mature B cells. B cell-activating factor belonging to the tumor necrosis factor family (BAFF) is another critical survival factor for B cells, and is also necessary for B cell maturation. Abnormal production of BAFF disturbs immune tolerance by allowing the survival of autoreactive B cells, thus triggering autoimmune disorders. BAFF can also have an important impact on B cell malignancies. In contrast to normal B cells, malignant B cells show uncontrolled cell proliferation. BAFF levels are elevated in the serum of patients with systemic autoimmune diseases, and, importantly, in patients with B-lymphoid malignancies. Furthermore, BAFF is produced by malignant B cells and acts as an essential autocrine survival factor. The strong dependence of certain lymphoid cancer cells on BAFF might be a point of vulnerability, which offers exciting new therapeutic possibilities.

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