Germinal centers (GC) are microanatomical structures critical for the development of high-affinity antibodies and B-cell memory. They are organised into two zones, light and dark, with coordinated roles, controlled by local signalling. 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. Here 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 (FDCs). 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.
Background: Receptor-ligand pairs of C-type lectin-like proteins have been shown to play an important role in cross talk between lymphocytes, as well as in immune responses within concrete tissues and structures, such as the skin or the germinal centres. The CD161-Lectin-like Transcript 1 (LLT1) pair has gained particular attention in recent years, yet a detailed analysis of LLT1 distribution in human tissue is lacking. One reason for this is the limited availability and poor characterisation of anti-LLT1 antibodies.
Methods: We assessed the staining capabilities of a novel anti-LLT1 antibody clone (2H7), both by immunohistochemistry and flow cytometry, showing its efficiency at LLT1 recognition in both settings. We then analysed LLT1 expression in a wide variety of human tissues.
Results: We found LLT1 expression in circulating B cells and monocytes, but not in lung and liver-resident macrophages. We found strikingly high LLT1 expression in immune-privileged sites, such as the brain, placenta and testes, and confirmed the ability of LLT1 to inhibit NK cell function.
Conclusions: Overall, this study contributes to the development of efficient tools for the study of LLT1. Moreover, its expression in different healthy human tissues and, particularly, in immune-privileged sites, establishes LLT1 as a good candidate as a regulator of immune responses.
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