Title: Circulating T-FH cells, serological memory, and tissue compartmentalization shape human influenza-specific B cell immunity
Authors: Koutsakos, M
Wheatley, AK
Loh, L
Clemens, EB
Sant, S
Nussing, 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
Issue Year: 2018
Publisher AMER ASSOC ADVANCEMENT SCIENCE
Series Sci. Transl. Med.:
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 (T-FH) 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, CD21(hi)CD27(+) memory B cells, and CD21(lo)CD27(+) B cells. Activation of circulating TFH cells correlated with the development of both CD21(lo) and CD21(hi) memory B cells. However, preexisting antibodies could limit increases in serum antibody titers. IIV had no marked effect on CD8(+), mucosal-associated invariant T, gamma delta 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 (CD21(hi)CD27(+)) 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.
URI: https://publications.svi.edu.au/publications/4599
Other Identifiers 10.1126/scitranslmed.aan8405
Publication type Article