000295847 001__ 295847
000295847 005__ 20250102134823.0
000295847 0247_ $$2doi$$a10.11588/HEIDOK.00035346
000295847 0247_ $$2URN$$ahttps://nbn-resolving.org/urn:nbn:de:bsz:16-heidok-353462
000295847 037__ $$aDKFZ-2024-02664
000295847 1001_ $$0P:(DE-He78)e74839b6d00040170cd36ad1b243979d$$aObraztsova, Anna$$b0$$gfemale$$udkfz
000295847 245__ $$aB cell fate decisions in vaccination: insights into germinal center and plasmablast responses
000295847 260__ $$bHeidelberg University Library$$c2024
000295847 3367_ $$2DataCite$$aOutput Types/Dissertation
000295847 3367_ $$2ORCID$$aDISSERTATION
000295847 3367_ $$2BibTeX$$aPHDTHESIS
000295847 3367_ $$02$$2EndNote$$aThesis
000295847 3367_ $$0PUB:(DE-HGF)11$$2PUB:(DE-HGF)$$aDissertation / PhD Thesis$$bphd$$mphd$$s1734096466_6325
000295847 3367_ $$2DRIVER$$adoctoralThesis
000295847 502__ $$aDissertation, Universität Heidelberg, 2024$$bDissertation$$cUniversität Heidelberg$$d2024$$o2024-07-26
000295847 520__ $$aHigh-affinity antibodies are a key component of protective immunity conferred by vaccines. They are developed through a process termed affinity maturation, relying on the natural selection of B cells with the strongest antigen-binding capacities within specialized structures called germinal centers. However, B cells can also undergo an alternative fate upon antigen encounter, differentiating into short-lived antibody-secreting cells called plasmablasts. These cells produce low-affinity antibodies and wane within a few days, representing an undesirable outcome for vaccination. Despite its significant impact on vaccine efficacy, the precise factors governing the early B cell fate decisions remain incompletely understood.This study unveils the critical role of activation strength in dictating B cell fate choices through in vitro and mathematical modeling of B cell activation and flow cytometric and scRNA-seq analysis of B cells responding to vaccination in vivo. I demonstrate that a range of factors contributing to heightened activation, including high antigen valency, strong B-cell receptor (BCR) affinity, the absence of suppressive antibody feedback, or presence of robust non-BCR stimulation, all promote preferential recruitment of B cells into the plasmablast compartment.These findings extend the existing view that high BCR affinity is the main factor directing B cells towards the plasmablast fate. This work paves the way for novel vaccine strategies that optimize affinity maturation and generate long-lasting, high-affinity antibody responses.
000295847 536__ $$0G:(DE-HGF)POF4-314$$a314 - Immunologie und Krebs (POF4-314)$$cPOF4-314$$fPOF IV$$x0
000295847 588__ $$aDataset connected to DataCite
000295847 650_7 $$2Other$$a570 Life sciences
000295847 773__ $$a10.11588/HEIDOK.00035346
000295847 8564_ $$uhttp://www.ub.uni-heidelberg.de/archiv/35346
000295847 909CO $$ooai:inrepo02.dkfz.de:295847$$pVDB
000295847 9141_ $$y2024
000295847 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)e74839b6d00040170cd36ad1b243979d$$aDeutsches Krebsforschungszentrum$$b0$$kDKFZ
000295847 9131_ $$0G:(DE-HGF)POF4-314$$1G:(DE-HGF)POF4-310$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vImmunologie und Krebs$$x0
000295847 9201_ $$0I:(DE-He78)D130-20160331$$kD130$$lB-Zell-Immunologie$$x0
000295847 980__ $$aphd
000295847 980__ $$aVDB
000295847 980__ $$aI:(DE-He78)D130-20160331
000295847 980__ $$aUNRESTRICTED