in part by studies conducted during the initial funding period of this grant, suggests that immediate early exposure of B cells to infection-induced innate signals shape the responses of B cells. Little is known about the nature of these signals and the mechanisms by which they affect the B cell response. The working hypothesis to be tested here is that infection-induced local innate immune signals differentially regulate various B cell subsets involved in the induction of protective immunity to influenza virus infection. The long-term objective of the studies is to determine how respiratory tract immunity to viral infections is induced and regulated. The objective of this proposal is to determine the mechanisms by which innate immune signals, particularly type I IFN shape the quality and magnitude of antiviral B cell responses. This is based on studies during the last funding period which showed type I IFN as a major infection-induced B cell stimulus in regional lymph nodes within 2 days of infection. To achieve our objective three Specific Aims will be carried out.
Specific Aim #1 will determine the mechanisms by which direct IFNR-signals received by B cells affect the magnitude and protective capacity of individual B cell response components to influenza: B-1 cells, extrafollicular foci and germinal center responses.
Specific Aim #2 will determine the role of toll-like receptor (TLR) 3 and 7-mediated signals on antiviral B cell response regulation to influenza infection and their integration with stimuli provided by the B cell receptor and/or T cell help.
In Specific Aim #3 the effects of IFNR-mediated B cell stimulation on local CD4 T cell responses to influenza virus infection and particular the affects on CD40-CD40L mediated help will be investigated. In vitro and in vivo tests are aided by the use of virus-specific T cell receptor transgenic mice. Completion of these studies will contribute to a better understanding of the processes that regulate the induction of protective antiviral B cell responses to influenza virus. Project Description Page 6

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI051354-09
Application #
8197133
Study Section
Immunity and Host Defense Study Section (IHD)
Program Officer
Hauguel, Teresa M
Project Start
2007-12-15
Project End
2013-11-30
Budget Start
2011-12-01
Budget End
2013-11-30
Support Year
9
Fiscal Year
2012
Total Cost
$371,492
Indirect Cost
$123,583
Name
University of California Davis
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Baumgarth, Nicole (2016) B-1 Cell Heterogeneity and the Regulation of Natural and Antigen-Induced IgM Production. Front Immunol 7:324
Elsner, Rebecca A; Hastey, Christine J; Olsen, Kimberly J et al. (2015) Suppression of Long-Lived Humoral Immunity Following Borrelia burgdorferi Infection. PLoS Pathog 11:e1004976
Waffarn, Elizabeth E; Hastey, Christine J; Dixit, Neha et al. (2015) Infection-induced type I interferons activate CD11b on B-1 cells for subsequent lymph node accumulation. Nat Commun 6:8991
Baumgarth, Nicole; Waffarn, Elizabeth E; Nguyen, Trang T T (2015) Natural and induced B-1 cell immunity to infections raises questions of nature versus nurture. Ann N Y Acad Sci 1362:188-99
Nguyen, Trang T T; Elsner, Rebecca A; Baumgarth, Nicole (2015) Natural IgM prevents autoimmunity by enforcing B cell central tolerance induction. J Immunol 194:1489-502
Elsner, Rebecca A; Hastey, Christine J; Baumgarth, Nicole (2015) CD4+ T cells promote antibody production but not sustained affinity maturation during Borrelia burgdorferi infection. Infect Immun 83:48-56
Savage, Hannah P; Baumgarth, Nicole (2015) Characteristics of natural antibody-secreting cells. Ann N Y Acad Sci 1362:132-42
Yenson, Vanessa; Baumgarth, Nicole (2014) Purification and immune phenotyping of B-1 cells from body cavities of mice. Methods Mol Biol 1190:17-34
Priest, Stephen O; Baumgarth, Nicole (2013) The role of innate signals in B cell immunity to influenza virus. Front Biosci (Schol Ed) 5:105-17
Baumgarth, Nicole (2013) Innate-like B cells and their rules of engagement. Adv Exp Med Biol 785:57-66

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