Antibody-mediated feedback modulates interclonal competition in the germinal center.
| Publication Type | Academic Article |
| 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 | Immunity |
| Volume | 59 |
| Issue | 3 |
| Pagination | 734-745.e5 |
| Date Published | 02/24/2026 |
| ISSN | 1097-4180 |
| Keywords | Germinal Center, Plasma Cells, B-Lymphocytes, Cell Competition |
| Abstract | Antibodies generated by prior immune responses regulate B cell activation and germinal center (GC) access upon recall immunization. Here, we examined how antibodies produced by an ongoing immune response influence the outcomes of contemporaneous GCs. We developed a mouse model in which expression of the diphtheria toxin receptor from the Prdm1 locus is conditional on tamoxifen-dependent removal of a floxed stop cassette, enabling specific ablation of plasma cells (PCs) and antibodies elicited by an antigen of interest without affecting prior responses. Whereas antibody-mediated feedback was not required for affinity maturation, it modulated competition between B cells with different epitope specificities, specifically by reducing the abundance of clones that recognized the same epitopes as plasma cell-derived soluble antibodies. This form of feedback represents a mechanism by which antibodies can shape epitope specificity in ongoing GCs, with implications for our understanding of immunodominance and for vaccine design strategies aimed at steering GCs toward desired epitopes on complex antigens. |
| DOI | 10.1016/j.immuni.2026.01.008 |
| PubMed ID | 41742422 |
| PubMed Central ID | PMC13036807 |