Microbiology & Immunology - Research Publications

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Author: Kedzierska, Katherine × Author: Chung, Amy × Start date: 2018 × End date: 2019 ×

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    Circulating TFH cells, serological memory, and tissue compartmentalization shape human influenza-specific B cell immunity
    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 (AMER ASSOC ADVANCEMENT SCIENCE, 2018-02-14)
    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.