The Role of Age-Associated B Cells (ABC) in Combating Influenza Infection
Name:
Olivia Kugler-Umana-Dissertation ...
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2024-09-16
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Dissertation
Authors
Kugler-Umana, OliviaFaculty Advisor
Susan L. SwainAcademic Program
Immunology and MicrobiologyUMass Chan Affiliations
PathologyDocument Type
Doctoral DissertationPublication Date
2022-07-12
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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-p004Permanent Link to this Item
http://hdl.handle.net/20.500.14038/51119Rights
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10.13028/3eg7-p004