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Engineered Systems of the Germinal Center and Bone Marrow for Antigen-Specific B Cell Generation and Longevity
Engineered Systems of the Germinal Center and Bone Marrow for Antigen-Specific B Cell Generation and Longevity
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202105521
- ISBN
- 9798263343941
- DDC
- 500
- 서명/저자
- Engineered Systems of the Germinal Center and Bone Marrow for Antigen-Specific B Cell Generation and Longevity
- 발행사항
- [Sl] : Georgia Institute of Technology, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 215 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 87-05, Section: B.
- 주기사항
- Advisor: Roy, Krishnendu;Singh, Ankur.
- 학위논문주기
- Thesis (Ph.D.)--Georgia Institute of Technology, 2024.
- 초록/해제
- 요약Memory and plasma B cells, which are responsible for maintaining protective levels of antibodies in the serum, are generated following antigen exposure. Due to the crucial roles that B cells play in the immune system, understanding and controlling the function of B cells is important in the context of therapeutic development for vaccines, immunotherapies, and cell therapies. An obstacle to producing prophylactic or therapeutic plasma and memory B cells-based treatments is a poor understanding of the complex cues and microenvironments that lead to the robust expansion of high-affinity, antigen-specific B cells and the development of long-lived plasma cells. Mimicking this complex set of events needed for B cell activation in robust and controllable in vitro platforms could allow for a better understanding of the critical signals that are necessary to mature and maintain B cells.The objectives of this work are to 1) mimic the germinal center (GC) reaction using a biomaterials particle-based platform to mediate antigen-specific B cell activation and 2) model the maturation, maintenance, and dynamics of antibody secreting cells (ASCs) within a supportive bone marrow-on-a-chip microniche. In Aim 1, we present a particlebased in vitro GC that induces rapid B cell proliferation, efficient induction of the GC reaction, and IgG class-switching in both murine and human cells. We demonstrate the importance of antigen-presentation on lipid membranes using liposomes to mimic follicular dendritic cell membrane fragments. In Aim 2, we present a microphyisological human bone marrow model that allows for ASC maturation and use it to study the dynamics and interactions of ASCs with cellular and extracellular matrix components of the bone marrow niche. These results can be leveraged to generate long-lived, high-affinity memory cell populations more effectively and to design strategies to treat conditions where B cell processes are comprised, such as aging, cancers, and autoimmunity.
- 일반주제명
- Plasma
- 일반주제명
- Vaccines
- 일반주제명
- Dendritic cells
- 일반주제명
- Antigen presentation
- 일반주제명
- Antibodies
- 일반주제명
- Immunotherapy
- 일반주제명
- Mutation
- 일반주제명
- Immune system
- 일반주제명
- Bone marrow
- 일반주제명
- Flow cytometry
- 일반주제명
- Biomedical materials
- 일반주제명
- Immunoglobulins
- 일반주제명
- Lipids
- 일반주제명
- Apoptosis
- 일반주제명
- Cell growth
- 일반주제명
- Blood
- 일반주제명
- Biomedical engineering
- 일반주제명
- Cellular biology
- 일반주제명
- Immunology
- 일반주제명
- Materials science
- 기본자료저록
- Dissertations Abstracts International. 87-05B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■006m o d
■007cr#unu||||||||
■020 ▼a9798263343941
■035 ▼a(MiAaPQ)AAI32309612
■035 ▼a(MiAaPQ)GeorgiaTech77691
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a500
■1001 ▼aKramer, Liana Lynn.
■24510▼aEngineered Systems of the Germinal Center and Bone Marrow for Antigen-Specific B Cell Generation and Longevity
■260 ▼a[Sl]▼bGeorgia Institute of Technology▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a215 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 87-05, Section: B.
■500 ▼aAdvisor: Roy, Krishnendu;Singh, Ankur.
■5021 ▼aThesis (Ph.D.)--Georgia Institute of Technology, 2024.
■520 ▼aMemory and plasma B cells, which are responsible for maintaining protective levels of antibodies in the serum, are generated following antigen exposure. Due to the crucial roles that B cells play in the immune system, understanding and controlling the function of B cells is important in the context of therapeutic development for vaccines, immunotherapies, and cell therapies. An obstacle to producing prophylactic or therapeutic plasma and memory B cells-based treatments is a poor understanding of the complex cues and microenvironments that lead to the robust expansion of high-affinity, antigen-specific B cells and the development of long-lived plasma cells. Mimicking this complex set of events needed for B cell activation in robust and controllable in vitro platforms could allow for a better understanding of the critical signals that are necessary to mature and maintain B cells.The objectives of this work are to 1) mimic the germinal center (GC) reaction using a biomaterials particle-based platform to mediate antigen-specific B cell activation and 2) model the maturation, maintenance, and dynamics of antibody secreting cells (ASCs) within a supportive bone marrow-on-a-chip microniche. In Aim 1, we present a particlebased in vitro GC that induces rapid B cell proliferation, efficient induction of the GC reaction, and IgG class-switching in both murine and human cells. We demonstrate the importance of antigen-presentation on lipid membranes using liposomes to mimic follicular dendritic cell membrane fragments. In Aim 2, we present a microphyisological human bone marrow model that allows for ASC maturation and use it to study the dynamics and interactions of ASCs with cellular and extracellular matrix components of the bone marrow niche. These results can be leveraged to generate long-lived, high-affinity memory cell populations more effectively and to design strategies to treat conditions where B cell processes are comprised, such as aging, cancers, and autoimmunity.
■590 ▼aSchool code: 0078.
■650 4▼aPlasma
■650 4▼aVaccines
■650 4▼aDendritic cells
■650 4▼aAntigen presentation
■650 4▼aAntibodies
■650 4▼aImmunotherapy
■650 4▼aMutation
■650 4▼aImmune system
■650 4▼aTumor necrosis factor-TNF
■650 4▼aBone marrow
■650 4▼aFlow cytometry
■650 4▼aBiomedical materials
■650 4▼aImmunoglobulins
■650 4▼aLipids
■650 4▼aApoptosis
■650 4▼aCell growth
■650 4▼aBlood
■650 4▼aBiomedical engineering
■650 4▼aCellular biology
■650 4▼aImmunology
■650 4▼aMaterials science
■690 ▼a0541
■690 ▼a0379
■690 ▼a0982
■690 ▼a0794
■71020▼aGeorgia Institute of Technology.
■7730 ▼tDissertations Abstracts International▼g87-05B.
■790 ▼a0078
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17360417▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.


