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Sci Transl Med. 2018 Feb 14;10(428). pii: eaan8405. doi: 10.1126/scitranslmed.aan8405.

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

Author information

1
Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.
2
World Health Organization (WHO) Collaborating Centre for Reference and Research on Influenza, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
3
Seqirus, 63 Poplar Road, Parkville, Victoria 3052, Australia.
4
Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Heidelberg, Victoria 3084, Australia.
5
Immunology and Diabetes Unit, St Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia.
6
Lung Transplant Unit, Alfred Hospital, Melbourne, Victoria 3004, Australia.
7
Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia.
8
Chris O'Brien Lifehouse Cancer Centre, Royal Prince Alfred Hospital, Camperdown, New South Wales 2050, Australia.
9
Immunology Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
10
St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales 2052, Australia.
11
Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Victoria 3004, Australia.
12
ARC Centre for Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Parkville, Victoria 3010, Australia.
13
Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia. kkedz@unimelb.edu.au tho.nguyen@unimelb.edu.au.

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 (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.

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