Antibody-mediated feedback modulates interclonal competition in the germinal center.

Publication Type Preprint
Authors Barbulescu A, Bilanovic J, Langelaar T, Teetz A, Urnavicius L, Hobbs A, Shen J, Abrahamse N, de Carvalho R, Mesin L, Ferreira C, Bortolatto J, Victora G
Journal bioRxiv
Date Published 11/07/2025
ISSN 2692-8205
Abstract Serum antibodies from prior immune responses regulate B cell activation and germinal center (GC) access upon recall immunization. However, how antibodies produced by an ongoing immune response influence the outcomes of contemporaneous GCs is less clear. To explore this, we developed mouse models enabling the targeted ablation of plasma cells and antibodies produced by an immune response of interest, without affecting those produced homeostatically or by prior antigen encounters. Our findings show that, whereas antibody-mediated feedback is not required for affinity maturation, it can influence competition between B cells with different epitope specificities, specifically by reducing the abundance of clones that recognize the same epitopes as circulating antibodies. This modality of feedback represents a mechanism by which antibody responses can influence epitope specificity in ongoing GCs. These findings may therefore have implications for vaccination strategies aimed at steering clonal selection towards desired epitopes on complex antigens.
DOI 10.1101/2025.11.06.686519
PubMed ID 41280010
PubMed Central ID PMC12637549
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