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| 001 | 295847 | ||
| 005 | 20250102134823.0 | ||
| 024 | 7 | _ | |2 doi |a 10.11588/HEIDOK.00035346 |
| 024 | 7 | _ | |2 URN |a https://nbn-resolving.org/urn:nbn:de:bsz:16-heidok-353462 |
| 037 | _ | _ | |a DKFZ-2024-02664 |
| 100 | 1 | _ | |0 P:(DE-He78)e74839b6d00040170cd36ad1b243979d |a Obraztsova, Anna |b 0 |g female |u dkfz |
| 245 | _ | _ | |a B cell fate decisions in vaccination: insights into germinal center and plasmablast responses |
| 260 | _ | _ | |b Heidelberg University Library |c 2024 |
| 336 | 7 | _ | |2 DataCite |a Output Types/Dissertation |
| 336 | 7 | _ | |2 ORCID |a DISSERTATION |
| 336 | 7 | _ | |2 BibTeX |a PHDTHESIS |
| 336 | 7 | _ | |0 2 |2 EndNote |a Thesis |
| 336 | 7 | _ | |0 PUB:(DE-HGF)11 |2 PUB:(DE-HGF) |a Dissertation / PhD Thesis |b phd |m phd |s 1734096466_6325 |
| 336 | 7 | _ | |2 DRIVER |a doctoralThesis |
| 502 | _ | _ | |a Dissertation, Universität Heidelberg, 2024 |b Dissertation |c Universität Heidelberg |d 2024 |o 2024-07-26 |
| 520 | _ | _ | |a High-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. |
| 536 | _ | _ | |0 G:(DE-HGF)POF4-314 |a 314 - Immunologie und Krebs (POF4-314) |c POF4-314 |f POF IV |x 0 |
| 588 | _ | _ | |a Dataset connected to DataCite |
| 650 | _ | 7 | |2 Other |a 570 Life sciences |
| 773 | _ | _ | |a 10.11588/HEIDOK.00035346 |
| 856 | 4 | _ | |u http://www.ub.uni-heidelberg.de/archiv/35346 |
| 909 | C | O | |o oai:inrepo02.dkfz.de:295847 |p VDB |
| 910 | 1 | _ | |0 I:(DE-588b)2036810-0 |6 P:(DE-He78)e74839b6d00040170cd36ad1b243979d |a Deutsches Krebsforschungszentrum |b 0 |k DKFZ |
| 913 | 1 | _ | |0 G:(DE-HGF)POF4-314 |1 G:(DE-HGF)POF4-310 |2 G:(DE-HGF)POF4-300 |3 G:(DE-HGF)POF4 |4 G:(DE-HGF)POF |a DE-HGF |b Gesundheit |l Krebsforschung |v Immunologie und Krebs |x 0 |
| 914 | 1 | _ | |y 2024 |
| 920 | 1 | _ | |0 I:(DE-He78)D130-20160331 |k D130 |l B-Zell-Immunologie |x 0 |
| 980 | _ | _ | |a phd |
| 980 | _ | _ | |a VDB |
| 980 | _ | _ | |a I:(DE-He78)D130-20160331 |
| 980 | _ | _ | |a UNRESTRICTED |
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