title: LLT1 and CD161 Expression in Human Germinal Centers Promotes B Cell Activation and CXCR4 Downregulation.
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.
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, United Kindgom;
authors.forename: Alba
authors.initials: A
authors.lastname: Llibre
authors.affiliation: Medical Research Unit on Immunochemistry, Specialties Hospital, National Medical Centre "Siglo XXI," Mexican Institute for Social Security, 06720 Mexico City, Mexico;
authors.forename: Constantino
authors.initials: C
authors.lastname: López-Macías
authors.affiliation: Department of Histopathology, University College London, London WC1E 6JJ, United Kingdom;
authors.forename: Teresa
authors.initials: T
authors.lastname: Marafioti
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, United Kindgom;
authors.forename: Hema
authors.initials: H
authors.lastname: Mehta
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, United Kindgom;
authors.forename: Amy
authors.initials: A
authors.lastname: Partridge
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, United Kindgom;
authors.forename: Carina
authors.identifier: http://orcid.org/0000-0003-3315-9424
authors.initials: C
authors.lastname: Kanzig
authors.affiliation: 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;
authors.forename: Felice
authors.initials: F
authors.lastname: Rivellese
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, National Institute for Health Research, Oxford Biomedical Research Centre, University of Oxford, Oxford OX3 7LJ, United Kingdom;
authors.forename: Jacob D
authors.identifier: http://orcid.org/0000-0003-4916-800X
authors.initials: JD
authors.lastname: Galson
authors.affiliation: Newcastle University, Newcastle upon Tyne NE1 7RU, United Kingdom;
authors.forename: Lucy J
authors.initials: LJ
authors.lastname: Walker
authors.affiliation: Newcastle University, Newcastle upon Tyne NE1 7RU, United Kingdom;
authors.forename: Paul
authors.initials: P
authors.lastname: Milne
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, United Kindgom;
authors.forename: Rodney E
authors.initials: RE
authors.lastname: Phillips
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, National Institute for Health Research, Oxford Biomedical Research Centre, University of Oxford, Oxford OX3 7LJ, United Kingdom;
authors.forename: Dominic F
authors.initials: DF
authors.lastname: Kelly
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215; and.
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Freeman
authors.affiliation: 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.
authors.forename: Mohey Eldin
authors.initials: ME
authors.lastname: El Shikh
authors.affiliation: 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.
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
authors.affiliation: 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.
authors.forename: Christian B
authors.identifier: http://orcid.org/0000-0001-5299-9344
authors.initials: CB
authors.lastname: Willberg
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D015536:Down-Regulation; D005434:Flow Cytometry; D018858:Germinal Center / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000096:biosynthesis / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000276:immunology*
chemical_list: C400041:CLEC2D protein, human; C527276:CXCR4 protein, human; C527203:KLRB1 protein, human; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D019718:Receptors, CXCR4; D011956:Receptors, Cell Surface
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