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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, 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.

Type Journal
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
Published Pages 1-15
Status Published in-print
DOI 10.1126/scitranslmed.aan8405
URL link to publisher's version