Zaretsky Irina, Atrakchi Ofir, Mazor Roei D, Stoler-Barak Liat, Biram Adi, Feigelson Sara W, Gitlin Alexander D, Engelhardt Britta, Shulman Ziv
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY.
J Exp Med. 2017 Nov 6;214(11):3435-3448. doi: 10.1084/jem.20171129. Epub 2017 Sep 22.
The germinal center (GC) reaction begins with a diverse and expanded group of B cell clones bearing a wide range of antibody affinities. During GC colonization, B cells engage in long-lasting interactions with T follicular helper (Tfh) cells, a process that depends on antigen uptake and antigen presentation to the Tfh cells. How long-lasting T-B interactions and B cell clonal expansion are regulated by antigen presentation remains unclear. Here, we use in vivo B cell competition models and intravital imaging to examine the adhesive mechanisms governing B cell selection for GC colonization. We find that intercellular adhesion molecule 1 (ICAM-1) and ICAM-2 on B cells are essential for long-lasting cognate Tfh-B cell interactions and efficient selection of low-affinity B cell clones for proliferative clonal expansion. Thus, B cell ICAMs promote efficient antibody immune response by enhancement of T cell help to cognate B cells.
生发中心(GC)反应始于一群多样化且扩增的B细胞克隆,这些克隆具有广泛的抗体亲和力。在GC定殖过程中,B细胞与滤泡辅助性T(Tfh)细胞进行持久的相互作用,这一过程依赖于抗原摄取以及向Tfh细胞呈递抗原。抗原呈递如何调节持久的T - B相互作用和B细胞克隆扩增仍不清楚。在这里,我们使用体内B细胞竞争模型和活体成像来研究控制B细胞选择进入GC定殖的黏附机制。我们发现B细胞上的细胞间黏附分子1(ICAM - 1)和ICAM - 2对于持久的同源Tfh - B细胞相互作用以及有效选择低亲和力B细胞克隆进行增殖性克隆扩增至关重要。因此,B细胞ICAMs通过增强T细胞对同源B细胞的辅助作用来促进有效的抗体免疫反应。