TY - JOUR
T1 - Circulating TFH cells, serological memory, and tissue compartmentalization shape human influenza-specific B cell immunity
AU - Koutsakos, Marios
AU - Wheatley, Adam K.
AU - Loh, Liyen
AU - Clemens, E. Bridie
AU - Sant, Sneha
AU - Nüssing, Simone
AU - Fox, Annette
AU - Chung, Amy W.
AU - Laurie, Karen L.
AU - Hurt, Aeron C.
AU - Rockman, Steve
AU - Lappas, Martha
AU - Loudovaris, Thomas
AU - Mannering, Stuart I.
AU - Westall, Glen P.
AU - Elliot, Michael
AU - Tangye, Stuart G.
AU - Wakim, Linda M.
AU - Kent, Stephen J.
AU - Nguyen, Thi H.O.
AU - Kedzierska, Katherine
N1 - Publisher Copyright:
Copyright © 2018 The Authors., some rights reserved.
PY - 2018/2/14
Y1 - 2018/2/14
N2 - 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, gd 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.
AB - 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, gd 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.
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U2 - 10.1126/scitranslmed.aan8405
DO - 10.1126/scitranslmed.aan8405
M3 - Article
C2 - 29444980
AN - SCOPUS:85042110429
SN - 1946-6234
VL - 10
JO - Science translational medicine
JF - Science translational medicine
IS - 428
M1 - eaan8405
ER -