Agnostic B cell selection approach identifies antibodies against K. pneumoniae that synergistically drive complement activation.

Suzan Rooijakkers, Sjors van der Lans,Bart Bardoel,Priscilla Kerkman,Maartje Ruyken,Carla de Haas, Stan Baijens,Remy Muts, Lisette Scheepmaker,Piet Aerts, Marije Van 't Wout, Renoud Marijnissen, Janine Schuurman,Frank Beurskens

crossref(2024)

引用 0|浏览1
暂无评分
摘要
Abstract Antibody-dependent complement activation plays a key role in the natural human immune response to infections. Currently, the understanding of which antibody-antigen combinations drive a potent complement response on bacteria is limited. Here, we develop an antigen-agnostic approach to stain and single-cell sort human IgG memory B cells recognizing intact bacterial cells, keeping surface antigens in their natural context. With this method we successfully identified 29 unique antibodies against K. pneumoniae, a dominant cause of hospital-acquired infections with increasing antibiotic resistance. Combining genetic tools and functional analyses, we reveal that the capacity of antibodies to activate complement on K. pneumoniae critically depends on their antigenic target. Furthermore, we find that certain antibody combinations can act synergistically to activate complement on K. pneumoniae. Understanding the molecular basis of effective complement activation by monoclonals or combining antibodies to mimic a polyclonal response could accelerate the development of antibody-based therapies against problematic infections.
更多
查看译文
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要