LLT1 and CD161 Expression in Human Germinal Centers Promotes B Cell Activation and CXCR4 Downregulation

人类生发中心中的 LLT1 和 CD161 表达促进 B 细胞活化和 CXCR4 下调

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作者:Alba Llibre, Constantino López-Macías, Teresa Marafioti, Hema Mehta, Amy Partridge, Carina Kanzig, Felice Rivellese, Jacob D Galson, Lucy J Walker, Paul Milne, Rodney E Phillips, Dominic F Kelly, Gordon J Freeman, Mohey Eldin El Shikh, Paul Klenerman, Christian B Willberg

Abstract

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.

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