The B-cell Activating Factor, commonly known as BAFF, is a protein that plays a role in the body’s immune system. This molecule is a cytokine belonging to the tumor necrosis factor (TNF) ligand family. BAFF is expressed in various cells, including monocytes, dendritic cells, and bone marrow stromal cells, and is important for maintaining immune balance.
BAFF Protein’s Role in Immune Health
BAFF is an important cytokine that helps regulate both innate and adaptive immune responses. It is particularly important for the development, survival, and maturation of B cells, which are specialized white blood cells responsible for producing antibodies that fight off infections. BAFF directly influences B cell survival by promoting the upregulation of anti-apoptotic proteins, such as Bcl-2 and Bcl-xL.
The protein interacts with three specific receptors found on B cells: BAFF receptor (BAFF-R), transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), and B cell maturation protein (BCMA). The interaction between BAFF and these receptors orchestrates various aspects of B cell biology, including their proliferation and differentiation into antibody-secreting plasma cells. Proper BAFF function ensures that B cells mature correctly and contribute to a balanced immune response.
BAFF and Autoimmune Disorders
When BAFF levels become imbalanced or excessive, it can contribute to the development of autoimmune diseases. Overactivity of BAFF can promote the survival and activation of self-reactive B cells, which are immune cells that mistakenly target the body’s own healthy tissues. These self-reactive B cells then produce autoantibodies, leading to chronic inflammation and tissue damage. Increased serum levels of BAFF are commonly observed in individuals with various autoimmune conditions.
Systemic Lupus Erythematosus (SLE) is an example where BAFF plays a role; elevated BAFF levels are often correlated with increased autoantibody titers and disease activity in SLE patients. Mice with overexpression of BAFF develop a lupus-like illness, characterized by the production of anti-DNA antibodies and kidney inflammation. Increased BAFF levels are also found in the synovial fluid of patients with Rheumatoid Arthritis, potentially prolonging the survival of disease-causing B cells. Sjögren’s Syndrome also shows elevated BAFF expression in salivary glands.
Therapeutic Approaches Targeting BAFF
Understanding BAFF’s involvement in autoimmune diseases has paved the way for targeted therapeutic interventions. These therapies aim to block or neutralize excessive BAFF, thereby reducing the overactivity of B cells and mitigating autoimmune symptoms. This approach aims to restore a healthy immune balance by limiting the survival of autoreactive B cells and decreasing autoantibody production. In animal models of autoimmunity, BAFF antagonism has led to a reduction in B cell numbers, decreased activation of T cells and dendritic cells, and an overall reduction in inflammation.
Belimumab, a fully human monoclonal antibody, is an approved therapeutic agent that specifically targets and inhibits BAFF. It works by neutralizing BAFF, which in turn inhibits the survival and differentiation of B cells. Clinical trials and preclinical data have demonstrated that belimumab can improve symptoms and reduce disease activity in patients with Systemic Lupus Erythematosus. Other BAFF inhibitors are also under development and show promise in managing conditions like Rheumatoid Arthritis, especially in patients who do not respond well to conventional treatments.