Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Curr Opin Immunol. 2021 Aug;71:75-80. doi: 10.1016/j.coi.2021.06.009. Epub 2021 Jun 26.
B cell activating factor (BAFF or BLyS), an important cytokine for B cell survival and humoral immune responses, is targeted in the clinic for the treatment of systemic lupus erythematosus. This review focuses on the structure, function and inhibition profiles of membrane-bound BAFF, soluble BAFF 3-mer and soluble BAFF 60-mer, all of which have distinct properties. BAFF contains a loop region not required for receptor binding but essential for receptor activation via promotion of BAFF-to-BAFF contacts. This loop region additionally allows formation of BAFF 60-mer, in which epitopes of the BAFF inhibitor belimumab are inaccessible. If 60-mer forms in humans, it is predicted to be short-lived and to act locally because adult serum contains a BAFF 60-mer dissociating activity. Cord blood contains elevated levels of BAFF, part of which displays attributes of 60-mer, suggesting a role for this form of BAFF in the development of foetal or neonate B cells.
B 细胞激活因子（BAFF 或 BLyS）是一种重要的细胞因子，可促进 B 细胞存活和体液免疫应答，目前临床上将其作为治疗系统性红斑狼疮的靶点。本综述重点介绍了膜结合型 BAFF、可溶性 BAFF 三聚体和可溶性 BAFF 六聚体的结构、功能和抑制特性，它们都具有独特的性质。BAFF 包含一个环区，该环区对于受体结合不是必需的，但对于通过促进 BAFF 与 BAFF 接触来激活受体是必需的。这个环区还允许形成 BAFF 六聚体，其中 BAFF 抑制剂贝利尤单抗的表位不可接近。如果 60 聚体在人体内形成，预计其半衰期短且作用局限，因为成人血清中含有一种可使 BAFF 60 聚体解离的活性物质。脐血中含有高水平的 BAFF，其中一部分表现出 60 聚体的特征，这表明这种形式的 BAFF 在胎儿或新生儿 B 细胞的发育中发挥作用。
