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CXCL13 is a plasma biomarker of germinal center activity.

Publication ,  Journal Article
Havenar-Daughton, C; Lindqvist, M; Heit, A; Wu, JE; Reiss, SM; Kendric, K; Bélanger, S; Kasturi, SP; Landais, E; Akondy, RS; McGuire, HM ...
Published in: Proc Natl Acad Sci U S A
March 8, 2016

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.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

March 8, 2016

Volume

113

Issue

10

Start / End Page

2702 / 2707

Location

United States

Related Subject Headings

  • Vaccination
  • Mice, Inbred C57BL
  • Macaca
  • Lymph Nodes
  • Humans
  • HIV Infections
  • Germinal Center
  • Flow Cytometry
  • Enzyme-Linked Immunosorbent Assay
  • Cohort Studies
 

Citation

APA
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ICMJE
MLA
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Havenar-Daughton, C., Lindqvist, M., Heit, A., Wu, J. E., Reiss, S. M., Kendric, K., … Crotty, S. (2016). CXCL13 is a plasma biomarker of germinal center activity. Proc Natl Acad Sci U S A, 113(10), 2702–2707. https://doi.org/10.1073/pnas.1520112113
Havenar-Daughton, Colin, Madelene Lindqvist, Antje Heit, Jennifer E. Wu, Samantha M. Reiss, Kayla Kendric, Simon Bélanger, et al. “CXCL13 is a plasma biomarker of germinal center activity.Proc Natl Acad Sci U S A 113, no. 10 (March 8, 2016): 2702–7. https://doi.org/10.1073/pnas.1520112113.
Havenar-Daughton C, Lindqvist M, Heit A, Wu JE, Reiss SM, Kendric K, et al. CXCL13 is a plasma biomarker of germinal center activity. Proc Natl Acad Sci U S A. 2016 Mar 8;113(10):2702–7.
Havenar-Daughton, Colin, et al. “CXCL13 is a plasma biomarker of germinal center activity.Proc Natl Acad Sci U S A, vol. 113, no. 10, Mar. 2016, pp. 2702–07. Pubmed, doi:10.1073/pnas.1520112113.
Havenar-Daughton C, Lindqvist M, Heit A, Wu JE, Reiss SM, Kendric K, Bélanger S, Kasturi SP, Landais E, Akondy RS, McGuire HM, Bothwell M, Vagefi PA, Scully E, IAVI Protocol C Principal Investigators, Tomaras GD, Davis MM, Poignard P, Ahmed R, Walker BD, Pulendran B, McElrath MJ, Kaufmann DE, Crotty S. CXCL13 is a plasma biomarker of germinal center activity. Proc Natl Acad Sci U S A. 2016 Mar 8;113(10):2702–2707.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

March 8, 2016

Volume

113

Issue

10

Start / End Page

2702 / 2707

Location

United States

Related Subject Headings

  • Vaccination
  • Mice, Inbred C57BL
  • Macaca
  • Lymph Nodes
  • Humans
  • HIV Infections
  • Germinal Center
  • Flow Cytometry
  • Enzyme-Linked Immunosorbent Assay
  • Cohort Studies