Llibre Alba, López-Macías Constantino, Marafioti Teresa, Mehta Hema, Partridge Amy, Kanzig Carina, Rivellese Felice, Galson Jacob D, Walker Lucy J, Milne Paul, Phillips Rodney E, Kelly Dominic F, Freeman Gordon J, El Shikh Mohey Eldin, Klenerman Paul, Willberg Christian B
Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, United Kindgom;
Medical Research Unit on Immunochemistry, Specialties Hospital, National Medical Centre "Siglo XXI," Mexican Institute for Social Security, 06720 Mexico City, Mexico;
J Immunol. 2016 Mar 1;196(5):2085-94. doi: 10.4049/jimmunol.1502462. Epub 2016 Feb 1.
Germinal centers (GCs) are microanatomical structures critical for the development of high-affinity Abs and B cell memory. They are organized into two zones, light and dark, with coordinated roles, controlled by local signaling. The innate lectin-like transcript 1 (LLT1) is known to be expressed on B cells, but its functional role in the GC reaction has not been explored. In this study, we report high expression of LLT1 on GC-associated B cells, early plasmablasts, and GC-derived lymphomas. LLT1 expression was readily induced via BCR, CD40, and CpG stimulation on B cells. Unexpectedly, we found high expression of the LLT1 ligand, CD161, on follicular dendritic cells. Triggering of LLT1 supported B cell activation, CD83 upregulation, and CXCR4 downregulation. Overall, these data suggest that LLT1-CD161 interactions play a novel and important role in B cell maturation within the GC in humans.
生发中心（GCs）是对高亲和力抗体和B细胞记忆的发育至关重要的微解剖结构。它们被组织成两个区域，即亮区和暗区，具有协调作用，受局部信号控制。已知天然凝集素样转录本1（LLT1）在B细胞上表达，但其在GC反应中的功能作用尚未被探索。在本研究中，我们报道LLT1在GC相关B细胞、早期浆母细胞和GC来源的淋巴瘤上高表达。通过BCR、CD40和CpG刺激可在B细胞上轻易诱导LLT1表达。出乎意料的是，我们发现滤泡树突状细胞上LLT1配体CD161高表达。LLT1的触发支持B细胞活化、CD83上调和CXCR4下调。总体而言，这些数据表明LLT1-CD161相互作用在人类GC内B细胞成熟中发挥着新的重要作用。
