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

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

Author information

1
Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, United Kindgom;
2
Medical Research Unit on Immunochemistry, Specialties Hospital, National Medical Centre "Siglo XXI," Mexican Institute for Social Security, 06720 Mexico City, Mexico;
3
Department of Histopathology, University College London, London WC1E 6JJ, United Kingdom;
4
Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, United Kingdom;
5
Oxford Vaccine Group, Department of Paediatrics, National Institute for Health Research, Oxford Biomedical Research Centre, University of Oxford, Oxford OX3 7LJ, United Kingdom;
6
Newcastle University, Newcastle upon Tyne NE1 7RU, United Kingdom;
7
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215; and.
8
Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, United Kingdom; chris.willberg@ndm.ox.ac.uk m.elshikh@qmul.ac.uk.
9
Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, United Kindgom; Oxford National Institute for Health Research Biomedical Research Centre, Oxford OX3 9DU, United Kingdom.
10
Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, United Kindgom; Oxford National Institute for Health Research Biomedical Research Centre, Oxford OX3 9DU, United Kingdom chris.willberg@ndm.ox.ac.uk m.elshikh@qmul.ac.uk.

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.

PMID:
26829983
PMCID:
PMC4760235
DOI:
10.4049/jimmunol.1502462
[Indexed for MEDLINE]
Free PMC Article

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