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

J Immunol. 2016 Mar 1;196(5):2085-94. doi: 10.4049/jimmunol.1502462. Epub 2016 Feb 1.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Cell Separation
  • Down-Regulation
  • Flow Cytometry
  • Germinal Center / immunology*
  • Humans
  • Immunohistochemistry
  • Lectins, C-Type / biosynthesis
  • Lectins, C-Type / immunology*
  • Lymphocyte Activation / immunology*
  • NK Cell Lectin-Like Receptor Subfamily B / biosynthesis
  • NK Cell Lectin-Like Receptor Subfamily B / immunology*
  • Real-Time Polymerase Chain Reaction
  • Receptors, CXCR4 / biosynthesis
  • Receptors, CXCR4 / immunology*
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Cell Surface / immunology*

Substances

  • CLEC2D protein, human
  • CXCR4 protein, human
  • KLRB1 protein, human
  • Lectins, C-Type
  • NK Cell Lectin-Like Receptor Subfamily B
  • Receptors, CXCR4
  • Receptors, Cell Surface