Colin Havenar‐Daughton; Madelene Lindqvist; Antje Heit; Jennifer E. Wu; Samantha Reiss; Kayla Kendric; Simon Bélanger; Sudhir Pai Kasturi; Elise Landais; Rama Akondy; Helen M. McGuire; Marcella Bothwell; Parsia A. Vagefi; Eileen P. Scully; IAVI Protocol C Principal Investigators; Georgia D. Tomaras; Mark M. Davis; Pascal Poignard; Rafi Ahmed; Bruce D. Walker; Bali Pulendran; M. Juliana McElrath; Daniel E. Kaufmann; Shane Crotty; Matt A. Price; Jill Gilmour; Pat Fast; Anatoli Kamali; Eduard J. Sanders; Omu Onzala; Susan Allen; Eric Hunter; Etienne Karita; William Kilembe; Shabir Lakhi; Mubiana Inambao · 2016 · Proceedings of the National Academy of Sciences
Paper
Significantly higher levels of plasma CXCL13 [chemokine (C-X-C motif) 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 the monitoring 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.
Analysis
This study identifies CXCL13 as a potential plasma biomarker for germinal center activity, showing its levels correlate with GC activity and antibody responses in various models and human cohorts.
Discovery
Dietmar Rudolf Thal; Koen Poesen; Rik Vandenberghe; Steffi De Meyer
Nicholas J. Ashton; Wagner S. Brum; Guglielmo Di Molfetta; Andréa Lessa Benedet; Burak Arslan; Erin M. Jonaitis; Rebecca E. Langhough; Karly Alex Cody; Rachael E. Wilson; Cynthia M. Carlsson; Eugeen Vanmechelen; Laia Montoliu‐Gaya; Juan Lantero‐Rodriguez; Nesrine Rahmouni; Cécile Tissot; Jenna Stevenson; Stijn Servaes; Joseph Therriault; Tharick A. Pascoal; Alberto Lleó; Daniel Alcolea; Juan Fortea; Pedro Rosa‐Neto; Sterling C. Johnson; Andreas Jeromin; Kaj Blennow; Henrik Zetterberg
Charles Bernick; Guogen Shan; Aaron Ritter; Nicholas J. Ashton; Kaj Blennow; Juan Lantero‐Rodriguez; Anniina Snellman; Henrik Zetterberg
Fernando González‐Ortiz; Michael Turton; Przemysław R. Kac; Denis S. Smirnov; Enrico Premi; Roberta Ghidoni; Luisa Benussi; Valentina Cantoni; Claudia Saraceno; Jasmine Rivolta; Nicholas J. Ashton; Barbara Borroni; Douglas Galasko; Peter Harrison; Henrik Zetterberg; Kaj Blennow; Thomas K. Karikari
Oskar Hansson; Rebecca M. Edelmayer; Adam L. Boxer; María C. Carrillo; Michelle M. Mielke; Gil D. Rabinovici; Stephen Salloway; Reisa A. Sperling; Henrik Zetterberg; Charlotte E. Teunissen
Henrik Zetterberg; Kaj Blennow
Source record