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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 Gene...
Engineered Systems of the Germinal Center and Bone Marrow for Antigen-Specific B Cell Generation and Longevity

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자료유형  
 학위논문 서양
최종처리일시  
20260202105521
ISBN  
9798263343941
DDC  
500
저자명  
Kramer, Liana Lynn.
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  
Tumor necrosis factor-TNF
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
기타저자  
Georgia Institute of Technology.
기본자료저록  
Dissertations Abstracts International. 87-05B.
전자적 위치 및 접속  
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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.

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