BAFF receptor polymorphisms and deficiency in humans. (August 2021)

• Record Type: Journal Article
• Authors: Sevdali, Eirini; Block Saldana, Violeta; Speletas, Matthaios; Eibel, Hermann
• Is Part Of: Current opinion in immunology. Volume 71(2021)
• Page Start: 103
• Page End: 110
• Publication Date: 2021-08
• Subjects: Immunology -- Periodicals; Allergy -- Periodicals; Immunology -- Abstracts -- Periodicals; Allergy -- Abstracts -- Periodicals; 616.079
• DOI: 10.1016/j.coi.2021.06.008
• Languages: English
• ISSNs: 0952-7915

Abstract

Highlights: Inborn defects in BAFFR prevent full maturation of B cells, cause hypogammaglobulinemia and impair T-independent responses. Different from switched memory B cells, survival of naïve and marginal zone B cells depends on BAFFR-derived signals. BAFFR variants affecting receptor function contribute to the onset of immunodeficiency, autoimmunity and B cell lymphomas. Abstract : The BAFF-receptor (BAFFR) is a member of the TNF-receptor family. It is expressed only by B cells and binds BAFF as single ligand, which activates key signaling pathways regulating essential cellular functions, including survival, protein synthesis, and metabolic fitness. In humans, BAFFR deficiency interrupts B cell development at the transition from immature to mature B cells and causes B lymphopenia, hypogammaglobulinemia, and impaired humoral immune responses. Polymorphisms in TNFRSF13C gene affecting BAFFR oligomerization and signaling have been described in patients with immunodeficiency, autoimmunity and B cell lymphomas. Despite a uniform expression pattern of BAFFR in peripheral mature B cells, depletion of BAFF with neutralizing antibodies in patients with systemic lupus erythematosus does not affect the survival of switched memory B cells. These findings imply a distinct dependency of mature B cell subsets on BAFF/BAFFR interaction and highlight the contribution of BAFFR-derived signals in peripheral B cell development and homeostasis.