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

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

doi:10.4049/jimmunol.1502462

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.

Highlights

We report the expression and function of the innate receptor pairing, lectin-like transcript 1 (LLT1) and CD161, within the germinal center (GC) reaction in humans
Competition for Ag and T follicular helper (Tfh) cell help occurs within the light zone (LZ), whereas somatic hypermutation and proliferation are restricted to the dark zone (DZ)
LLT1 expression was marginally higher on DZ cells, it was observed on all GC B cells in all lymphoid tissues tested

Summary

Introduction

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. 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.

Results

Conclusion