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    The Role of Age-Associated B Cells (ABC) in Combating Influenza Infection

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    Name:
    Olivia Kugler-Umana-Dissertation ...
    Embargo:
    2024-09-16
    Size:
    4.469Mb
    Format:
    PDF
    Description:
    Dissertation
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    Authors
    Kugler-Umana, Olivia
    Faculty Advisor
    Susan L. Swain
    Academic Program
    Immunology and Microbiology
    UMass Chan Affiliations
    Pathology
    Document Type
    Doctoral Dissertation
    Publication Date
    2022-07-12
    Keywords
    influenza A virus (IAV) infection
    age-associated B cells
    
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    Abstract
    With age, follicular helper T cell (TFH) dependent B cell responses erode, reducing B cell memory and long-term antibody responses. However, aged mice and humans develop an alternative B cell population, termed age-associated B cells (ABC), that may produce TFH independent antibodies. ABC lack CD21 and CD23 expression, and some express transcription factors and adhesion molecules indicative of antigen exposure. Some of these have been implicated in autoimmunity. We found a unique population of responding B cells following influenza A virus (IAV) infection, which was Fashi/GL7neg. We postulated that the CD21-CD23-ABC might be progenitors of these non-follicular B cells, that we called induced ABC (iABC). Using T-deficient RAG KO and TFH deficient SAP KO hosts, we found that the CD21-CD23-ABC can become iABC (FasHiGL7-) upon IAV infection. These iABC share the same phenotype of iABC found in infected aged mice and can become Ab-producing cells without T cell help. We showed that CD21-CD23-ABC can be separated into IgD+ (putative naïve B cells) vs. IgD- (memory-like B cells). We followed their ability to become iABC in SAP KO hosts. The IgD+ABC were most efficient at giving rise to iABC. Further transfer studies revealed that iABC generation from donor IgD+ABC requires extrinsic TLR signaling, and IgD+ABC can provide Ab-medicated protection. We concluded that upon T-independent stimulation, IgD+ABC (CD21-CD23-) become iABC (Fashi/GL7neg), some of which can secrete IAV-specific Ab and may provide protection against IAV.
    DOI
    10.13028/3eg7-p004
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/51119
    Rights
    Copyright © 2022 Kugler-Umana.
    Distribution License
    All Rights Reserved
    ae974a485f413a2113503eed53cd6c53
    10.13028/3eg7-p004
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    Morningside Graduate School of Biomedical Sciences Dissertations and Theses

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