Sakai Jiro, Akkoyunlu Mustafa
Laboratory of Bacterial Polysaccharides, Division of Bacterial Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Laboratory of Bacterial Polysaccharides, Division of Bacterial Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA
Clin Microbiol Rev. 2017 Oct;30(4):991-1014. doi: 10.1128/CMR.00046-17.
The two ligands B cell-activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) and the three receptors BAFF receptor (BAFF-R), transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI), and B cell maturation antigen (BCMA) are members of the "BAFF system molecules." BAFF system molecules are primarily involved in B cell homeostasis. The relevance of BAFF system molecules in host responses to microbial assaults has been investigated in clinical studies and in mice deficient for each of these molecules. Many microbial products modulate the expression of these molecules. Data from clinical studies suggest a correlation between increased expression levels of BAFF system molecules and elevated B cell responses. Depending on the pathogen, heightened B cell responses may strengthen the host response or promote susceptibility. Whereas pathogen-mediated increases in the expression levels of the ligands and/or the receptors appear to promote microbial clearance, certain pathogens have evolved to ablate B cell responses by suppressing the expression of TACI and/or BAFF-R on B cells. Other than its well-established role in B cell responses, the TACI-mediated activation of macrophages is also implicated in resistance to intracellular pathogens. An improved understanding of the role that BAFF system molecules play in infection may assist in devising novel strategies for vaccine development.
肿瘤坏死因子家族的两种配体——B细胞活化因子（BAFF）和增殖诱导配体（APRIL），以及三种受体——BAFF受体（BAFF-R）、跨膜激活剂和钙调亲环素配体相互作用分子（TACI）和B细胞成熟抗原（BCMA），都是“BAFF系统分子”的成员。BAFF系统分子主要参与B细胞的稳态。临床研究以及针对这些分子各自缺陷的小鼠模型研究，都对BAFF系统分子在宿主对微生物攻击反应中的相关性进行了探究。许多微生物产物可调节这些分子的表达。临床研究数据表明，BAFF系统分子表达水平的升高与B细胞反应增强之间存在关联。根据病原体的不同，增强的B细胞反应可能会加强宿主反应，也可能会促进易感性。虽然病原体介导的配体和/或受体表达水平升高似乎有助于微生物清除，但某些病原体已经进化出通过抑制B细胞上TACI和/或BAFF-R的表达来消除B细胞反应的机制。除了在B细胞反应中已明确的作用外，TACI介导的巨噬细胞激活也与对细胞内病原体的抗性有关。更好地理解BAFF系统分子在感染中所起的作用，可能有助于设计新的疫苗开发策略。
