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


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, 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, gammadelta 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.

Type Journal
ISBN 1946-6242 (Electronic) 1946-6234 (Linking)
Authors Koutsakos, M.; Wheatley, A. K.; Loh, L.; Clemens, E. B.; Sant, S.; Nussing, S.; Fox, A.; Chung, A. W.; Laurie, K. L.; Hurt, A. C.; Rockman, S.; Lappas, M.; Loudovaris, T.; Mannering, S. I.; Westall, G. P.; Elliot, M.; Tangye, S. G.; Wakim, L. M.; Kent, S. J.; Nguyen, T. H. O.; Kedzierska, K.
Responsible Garvan Author Prof Stuart Tangye
Publisher Name Science Translational Medicine
Published Date 2018-02-14
Published Volume 10
Published Issue 428
Status Published in-print
DOI 10.1126/scitranslmed.aan8405
URL link to publisher's version