当前位置： SCI文献检索 > Science Translational Medicine期刊下所有文献 > Circulating TFH cells, serological memory, and tissue compartmentalization shape human influenza-specific B cell immunity.

Circulating TFH cells, serological memory, and tissue compartmentalization shape human influenza-specific B cell immunity.

Abstract：

:Immunization with the inactivated influenza vaccine (IIV) remains the most effective strategy to combat seasonal influenza infections. IIV activates B cells and T follicular helper (TFH) cells and thus engenders antibody-secreting cells and serum antibody titers. However, the cellular events preceding generation of protective immunity in humans are inadequately understood. We undertook an in-depth analysis of B cell and T cell immune responses to IIV in 35 healthy adults. Using recombinant hemagglutinin (rHA) probes to dissect the quantity, phenotype, and isotype of influenza-specific B cells against A/California09-H1N1, A/Switzerland-H3N2, and B/Phuket, we showed that vaccination induced a three-pronged B cell response comprising a transient CXCR5-CXCR3+ antibody-secreting B cell population, CD21hiCD27+ memory B cells, and CD21loCD27+ B cells. Activation of circulating TFH cells correlated with the development of both CD21lo and CD21hi memory B cells. However, preexisting antibodies could limit increases in serum antibody titers. IIV had no marked effect on CD8+, mucosal-associated invariant T, γδ T, and natural killer cell activation. In addition, vaccine-induced B cells were not maintained in peripheral blood at 1 year after vaccination. We provide a dissection of rHA-specific B cells across seven human tissue compartments, showing that influenza-specific memory (CD21hiCD27+) B cells primarily reside within secondary lymphoid tissues and the lungs. Our study suggests that a rational design of universal vaccines needs to consider circulating TFH cells, preexisting serological memory, and tissue compartmentalization for effective B cell immunity, as well as to improve targeting cellular T cell immunity.

journal_name

Sci Transl Med

journal_title

Science translational medicine

authors

Koutsakos M,Wheatley AK,Loh L,Clemens EB,Sant S,Nüssing S,Fox A,Chung AW,Laurie KL,Hurt AC,Rockman S,Lappas M,Loudovaris T,Mannering SI,Westall GP,Elliot M,Tangye SG,Wakim LM,Kent SJ,Nguyen THO,Kedzierska K

doi

10.1126/scitranslmed.aan8405

subject

Has Abstract

pub_date

2018-02-14 00:00:00

issue

428

eissn

1946-6234

issn

1946-6242

pii

10/428/eaan8405

journal_volume

pub_type

杂志文章

在线工具

Circulating TFH cells, serological memory, and tissue compartmentalization shape human influenza-specific B cell immunity.