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Affinity maturation of the B-cell repertoire

B 细胞库的亲和力成熟

基本信息

批准号：
10229503
负责人：
GARNETT H KELSOE
金额：
$ 36万
依托单位：
BOSTON CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-08-01 至 2023-04-06
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10229503
关键词：
Address Adjuvant Affinity Antibodies Antibody Binding Sites Antibody Formation Antigens Avidity B cell repertoire B-Lymphocytes Binding Bone Marrow Cell Compartmentation Cells Clone Cells Congenic Mice Development Epitopes Exposure to Feedback Generations Genes Genetic Head Hemagglutinin Human Immunity Immunization Immunize Immunoglobulin Class Switching Immunoglobulin G Immunoglobulin M Immunologic Memory Immunologics Individual Infection Influenza Influenza Hemagglutinin Influenza vaccination Injections Knock-in Lymphocyte Maintenance Memory B-Lymphocyte Methods Mus Mutate Mutation Population Population Dynamics Recombinants Recording of previous events Seasons Serum Specificity Structure Structure of germinal center of lymph node Vaccination Vaccines Virus cross reactivity design flu global health imprint infancy influenza infection novel response secondary lymphoid organ single cell analysis stem vaccine efficacy

项目摘要

Abstract Influenza infection or immunization elicit robust humoral responses but mutations that accumulate in the influenza virus hemagglutinin (HA) render both types of humoral responses seasonal: immunity against this season's flu does not reliably protect against next year's virus. Crucially, vaccine efficacy is influenced by each individual's history of infection and vaccination and this influence is long-lived and can be traced to the memory B cells compartments elicited by prior exposure to HA antigens. The immunological basis of this influence or clonal imprinting, is clonal dominance by memory B lymphocytes generated to cross-reactive HA antigens. Examples of clonal imprinting or original antigenic sin (OAS) have been well described, but the scope, durability, and structural constraints of imprinting have not been systematically studied. In project 2 we will use a novel method for large scale, single B-cell cloning to determine how and in which immunological compartments OAS is “stored” and to define the structural similarities of epitope and paratope necessary for imprinting. Two types of memory B cells are responsible for the maintenance of humoral immune memory, IgM+ memory B cells (IgM+ Bmem) that have not undergone class-switch and class-switched (e.g., IgG+) Bmem; these small, quiescent lymphocytes reside in secondary lymphoid organs, where they are efficiently exposed to antigens. The population structure and dynamics of these populations following exposure to influenza hemagglutinins (HAs) is the focus of Project 2..

摘要