The role of the BAFF/APRIL system in B cell homeostasis and lymphoid cancers.
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.
Mackay
Fabienne
F
The Garvan Institute of Medical Research, Department of Arthritis and Inflammation, 384 Victoria Street, Darlinghurst, NSW 2010, Australia. f.mackay@garvan.org.au
Tangye
Stuart G
SG
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015551:Autoimmunity; D053264:B-Cell Activating Factor; D001402:B-Lymphocytes / Q000502:physiology*; D004854:Herpesvirus 4, Human / Q000235:genetics; D006706:Homeostasis; D006801:Humans; D016393:Lymphoma, B-Cell / Q000209:etiology*; D008565:Membrane Proteins / Q000502:physiology*; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D000911:Antibodies, Monoclonal; D053264:B-Cell Activating Factor; D008565:Membrane Proteins; C114631:TNFSF13 protein, human; C505719:TNFSF13B protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha