Research Papers: Gerotarget (Focus on Aging):

BTLA expression declines on B cells of the aged and is associated with low responsiveness to the trivalent influenza vaccine

Senthil Kannan, Raj K. Kurupati, Susan A. Doyle, Gordon J. Freeman, Kenneth E. Schmader and Hildegund C.J. Ertl _

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Oncotarget. 2015; 6:19445-19455. https://doi.org/10.18632/oncotarget.4597

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Senthil Kannan1,2, Raj K. Kurupati2, Susan A. Doyle3, Gordon J. Freeman4, Kenneth E. Schmader3 and Hildegund C.J. Ertl2

1 Biomedical Graduate Group, University of Pennsylvania, Philadelphia, PA, USA

2 The Wistar Institute, Philadelphia, PA, USA

3 GRECC, Durham VA Medical Center and Center for the Study of Aging and Human, Development and Division of Geriatrics, Department of Medicine, Duke University Medical Center, Durham, NC, USA

4 Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

Correspondence to:

Hildegund C.J. Ertl, email:

Keywords: BTLA, aging, HSV, immunosenescence, influenza

Received: June 03, 2015 Accepted: June 11, 2015 Published: June 21, 2015


Virus-neutralizing antibody and B cell responses to influenza A viruses were measured in 35 aged and 28 middle-aged individuals following vaccination with the 2012 and 2013 trivalent inactivated influenza vaccines. Antibody responses to the vaccine strains were lower in the aged. An analysis of B cell subsets by flow cytometry with stains for immunoregulators showed that B cells of multiple subsets from the aged as compared to younger human subjects showed differences in the expression of the co-inhibitor B and T lymphocyte attenuator (BTLA). Expression of BTLA inversely correlated with age and appears to be linked to shifting the nature of the response from IgM to IgG. High BTLA expression on mature B cells was linked to higher IgG responses to the H1N1 virus. Finally, high BTLA expression on isotype switched memory B cells was linked to better preservation of virus neutralizing antibody titers and improved recall responses to vaccination given the following year.

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