Pauli Noel T, Kim Hwan Keun, Falugi Fabiana, Huang Min, Dulac John, Henry Dunand Carole, Zheng Nai-Ying, Kaur Kaval, Andrews Sarah F, Huang Yunping, DeDent Andrea, Frank Karen M, Charnot-Katsikas Angella, Schneewind Olaf, Wilson Patrick C
Committee on Immunology; Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research; Department of Microbiology; and Department of Pathology, The University of Chicago, Chicago, IL 60637 Committee on Immunology; Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research; Department of Microbiology; and Department of Pathology, The University of Chicago, Chicago, IL 60637.
Committee on Immunology; Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research; Department of Microbiology; and Department of Pathology, The University of Chicago, Chicago, IL 60637.
J Exp Med. 2014 Nov 17;211(12):2331-9. doi: 10.1084/jem.20141404. Epub 2014 Oct 27.
Staphylococcus aureus bacterial infection commonly results in chronic or recurrent disease, suggesting that humoral memory responses are hampered. Understanding how S. aureus subverts the immune response is critical for the rescue of host natural humoral immunity and vaccine development. S. aureus expresses the virulence factor Protein A (SpA) on all clinical isolates, and SpA has been shown in mice to expand and ablate variable heavy 3 (VH3) idiotype B cells. The effects of SpA during natural infection, however, have not been addressed. Acutely activated B cells, or plasmablasts (PBs), were analyzed to dissect the ongoing immune response to infection through the production of monoclonal antibodies (mAbs). The B cells that were activated by infection had a highly limited response. When screened against multiple S. aureus antigens, only high-affinity binding to SpA was observed. Consistently, PBs underwent affinity maturation, but their B cell receptors demonstrated significant bias toward the VH3 idiotype. These data suggest that the superantigenic activity of SpA leads to immunodominance, limiting host responses to other S. aureus virulence factors that would be necessary for protection and memory formation.
金黄色葡萄球菌感染通常会导致慢性或复发性疾病，这表明体液免疫记忆反应受到了阻碍。了解金黄色葡萄球菌如何破坏免疫反应对于恢复宿主天然体液免疫和疫苗开发至关重要。在所有临床分离株中，金黄色葡萄球菌都表达毒力因子A蛋白（SpA），并且在小鼠中已表明SpA可扩增和消除可变重链3（VH3）独特型B细胞。然而，SpA在自然感染过程中的作用尚未得到研究。通过分析急性活化的B细胞或浆母细胞（PB）来剖析通过产生单克隆抗体（mAb）对感染的持续免疫反应。被感染激活的B细胞反应非常有限。当针对多种金黄色葡萄球菌抗原进行筛选时，仅观察到与SpA的高亲和力结合。一致地，PB经历了亲和力成熟，但其B细胞受体对VH3独特型表现出明显的偏向性。这些数据表明，SpA的超抗原活性导致免疫优势，限制了宿主对其他对保护和记忆形成至关重要的金黄色葡萄球菌毒力因子的反应。
