CXCL13 is a plasma biomarker of germinal center activity

• Type of Material: Article
• Authors: Colin Havenar-Daughton, La Jolla Institute for Allergy and Immunology; Madelene Lindqvist, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla; Antje Heit, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla; Jennifer E. Wu, La Jolla Institute for Allergy and Immunology; Samantha M. Reiss, La Jolla Institute for Allergy and Immunology; Kayla Kendric, La Jolla Institute for Allergy and Immunology; Simon Belanger, La Jolla Institute for Allergy and Immunology; Sudhir Kasturi, Emory University; Elise Landais, International AIDS Vaccine Initiative, La Jolla; Rama Akondy, Emory University; Helen M. McGuire, Stanford University; Marcella Bothwell, University of California San Diego; Parsia A. Vagefi, Massachusetts General Hospital; Eileen Scully, Massachusetts Institute of Technology; Georgia D. Tomaras, Duke University; Mark M. Davis, Stanford University; Pascal Poignard, International AIDS Vaccine Initiative; Rafi Ahmed, Emory University; Bruce D. Walker, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla; Bali Pulendran, Emory University; M. Juliana McElrath, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla; Daniel E. Kaufmann, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla; Shane Crotty, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla
• Language: English
• Date: 2016-03-08
• Publisher: United States National Academy of Sciences
• Publication Version: Final Published Version
• Copyright Statement: © 2016 National Academy of Sciences.
• Final Published Version (URL): http://dx.doi.org/10.1073/pnas.1520112113
• Title of Journal or Parent Work: PNAS
• Volume: 113
• Issue: 10
• Start Page: 2702
• End Page: 2707
• Grant/Funding Information: None declared
• Keywords: Helper-cell differentiation; Dendritic Cells; Multidisciplinary Sciences; Science & Technology; Lymphoid tissue; HIV; Vaccine; Serum levels; Science & Technology - Other Topics; Neutralizing antibodies; CD4 T-Cells; vaccines; CXCL13; Chemokine CXCL13; Tfh; BCL6; antibodies; Antibody responses
• Research Categories: Biology, Cell; Health Sciences, Medicine and Surgery; Biology, Microbiology; Health Sciences, Immunology

Abstract

Significantly higher levels of plasma CXCL13 [chemokine (C-X-Cmotif) ligand 13] were associated with the generation of broadly neutralizing antibodies (bnAbs) against HIV in a large longitudinal cohort of HIV-infected individuals. Germinal centers (GCs) perform the remarkable task of optimizing B-cell Ab responses. GCs are required for almost all B-cell receptor affinity maturation and will be a critical parameter to monitor if HIV bnAbs are to be induced by vaccination. However, lymphoid tissue is rarely available from immunized humans,making themonitoring of GC activity by direct assessment of GC B cells and germinal center CD4+ T follicular helper (GC Tfh) cells problematic. The CXCL13-CXCR5 [chemokine (C-X-C motif) receptor 5] chemokine axis plays a central role in organizing both B-cell follicles and GCs. Because GC Tfh cells can produce CXCL13, we explored the potential use of CXCL13 as a blood biomarker to indicate GC activity. In a series of studies, we found that plasma CXCL13 levels correlated with GC activity in draining lymph nodes of immunized mice, immunized macaques, and HIV-infected humans. Furthermore, plasma CXCL13 levels in immunized humans correlated with the magnitude of Ab responses and the frequency of ICOS+ (inducible T-cell costimulator) Tfh-like cells in blood. Together, these findings support the potential use of CXCL13 as a plasma biomarker of GC activity in human vaccine trials and other clinical settings.