eprintid: 35346
rev_number: 18
eprint_status: archive
userid: 7810
dir: disk0/00/03/53/46
datestamp: 2024-09-02 13:43:38
lastmod: 2024-09-03 15:29:48
status_changed: 2024-09-02 13:43:38
type: doctoralThesis
metadata_visibility: show
creators_name: Obraztsova, Anna
title: B cell fate decisions in vaccination: insights into germinal center and plasmablast responses
subjects: ddc-570
divisions: i-140001
adv_faculty: af-14
cterms_swd: Immunologie
cterms_swd: Antikörper
cterms_swd: Impfstoff
abstract: 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.
date: 2025
id_scheme: DOI
id_number: 10.11588/heidok.00035346
own_urn: urn:nbn:de:bsz:16-heidok-353462
date_accepted: 2024-07-26
advisor: HASH(0x559de76e6aa8)
language: eng
bibsort: OBRAZTSOVABCELLFATED20250823
full_text_status: restricted
place_of_pub: Heidelberg
citation:   Obraztsova, Anna  (2025) B cell fate decisions in vaccination: insights into germinal center and plasmablast responses.  [Dissertation]     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/35346/1/Dissertation_Anna_Obraztsova.pdf