التفاصيل البيبلوغرافية
| العنوان: |
Role of poly/autoreactive B cells in the protective immune response, The |
| المؤلفون: |
Agazio, Amanda |
| المساهمون: |
Torres, Raul M., van Dyk, Linda, Cambier, John, Marrack, Pippa, Santiago, Mario L., Hagman, James |
| بيانات النشر: |
University of Colorado at Denver, Anschutz Medical Campus. Health Sciences Library |
| سنة النشر: |
2020 |
| المجموعة: |
Digital Collections of Colorado (Colorado State University) |
| مصطلحات موضوعية: |
polyreactive, autoreactive, Peripheral Tolerance, HIV-1, B-Lymphocytes, Broadly Neutralizing Antibodies |
| الوصف: |
Includes bibliographical references. ; Summer ; Peripheral tolerance is essential for silencing weakly autoreactive B cells that have escaped central tolerance, but it is unclear why these potentially pathogenic B cells are retained rather than being eliminated entirely. Release from peripheral tolerance can occur under certain circumstances (i.e. strong TLR stimulus), that are present during infection. In this regard, we hypothesized that autoreactive B cells could function as a reserve population that can be activated to contribute to the humoral immune response, particularly with pathogens, such as HIV-1, that exploit immune tolerance to avoid host defense. In this dissertation, I identified a population of autoreactive B cells with the potential to neutralize HIV-1 and designed approaches to experimentally release them from the functional restrictions of peripheral tolerance. Our lab had previously identified murine monoclonal antibodies that displayed autoreactivity against histone H2A and neutralized HIV-1 in vitro. Here, I generated additional H2A-reactive IgM monoclonal antibodies and demonstrate that they are both autoreactive and polyreactive with self and foreign antigens and are able to neutralize multiple clades of tier 2 HIV-1. Flow cytometric analysis of H2A-reactive B cells in naïve wildtype mice revealed that these B cells are present in peripheral B cell populations. I also demonstrated that murine H2A-reactive B cells are restrained by tolerance mechanisms. Specifically, H2A-reactive B cells do not produce antibody following immunization, fail to mobilize calcium upon immunoreceptor stimulation, and express inhibitory mediators associated with B cell anergy. Moreover, I show that toll-like receptor stimulation or provision of CD4 T cell help induces the in vitro production of H2A-reactive antibodies, breaking tolerance. Thus, this dissertation describes a novel poly/autoreactive B cell population that has the potential to neutralize HIV-1 but is silenced by immune tolerance, suggesting ... |
| نوع الوثيقة: |
text |
| وصف الملف: |
born digital; doctoral dissertations; application/pdf |
| اللغة: |
English |
| العلاقة: |
2017 to Current; Agazio_ucdenveramc_1639D_10737.pdf; https://hdl.handle.net/10968/5737Test |
| الإتاحة: |
https://hdl.handle.net/10968/5737Test |
| حقوق: |
Copyright of the original work is retained by the author. |
| رقم الانضمام: |
edsbas.1236A69C |
| قاعدة البيانات: |
BASE |
