CXCL13 is a plasma biomarker of germinal center activity

被引：272

作者：

Havenar-Daughton, Colin ^{[1
,2
]}

Lindqvist, Madelene ^{[2
,3
,4
]}

Heit, Antje ^{[2
,5
]}

Wu, Jennifer E. ^{[1
]}

Reiss, Samantha M. ^{[1
]}

Kendric, Kayla ^{[1
]}

Belanger, Simon ^{[1
]}

Kasturi, Sudhir Pai ^{[6
,7
]}

Landais, Elise

Akondy, Rama S. ^{[7
]}

McGuire, Helen M. ^{[9
]}

Bothwell, Marcella ^{[10
,11
]}

Vagefi, Parsia A. ^{[12
]}

Scully, Eileen ^{[3
,4
]}

Tomaras, Georgia D. ^{[14
]}

Davis, Mark M. ^{[9
,15
]}

Poignard, Pascal ^{[8
,16
]}

Ahmed, Rafi ^{[2
,7
]}

Walker, Bruce D. ^{[2
,3
,4
,17
]}

Pulendran, Bali ^{[2
,6
,7
]}

McElrath, M. Juliana ^{[2
,5
]}

Kaufmann, Daniel E. ^{[2
,3
,4
,18
,19
]}

Crotty, Shane ^{[1
,2
]}

机构：

[1] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA 92037 USA

[2] Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA

[3] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02114 USA

[4] Harvard Univ, Boston, MA USA

[5] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA

[6] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA

[7] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA

[8] Int AIDS Vaccine Initiat, Neutralizing Antibody Ctr, La Jolla, CA 92037 USA

[9] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94304 USA

[10] Univ Calif San Diego, Dept Surg, San Diego, CA 92123 USA

[11] Rady Childrens Hosp San Diego, Pediat Otolaryngol, San Diego, CA 92123 USA

[12] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA

[13] Int AIDS Vaccine Initiat, New York, NY 10038 USA

[14] Duke Univ, Sch Med, Duke Human Vaccine Inst, Durham, NC 27710 USA

[15] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94304 USA

[16] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA

[17] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

[18] Univ Montreal, Dept Med, Montreal, PQ H2X 0A9, Canada

[19] CRCHUM, Montreal, PQ H2X 0A9, Canada

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2016年 / 113卷 / 10期

关键词：

vaccines; CXCL13; HIV; antibodies; Tfh; HELPER-CELL DIFFERENTIATION; CD4; T-CELLS; ANTIBODY-RESPONSES; CHEMOKINE CXCL13; NEUTRALIZING ANTIBODIES; LYMPHOID FOLLICLES; DENDRITIC CELLS; SERUM-LEVELS; VACCINE; BCL6;

D O I：

10.1073/pnas.1520112113

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 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.

引用

页码：2702 / 2707

页数：6

共 50 条

[1] Germinal-center organization and cellular dynamics [J].