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Selective clonal attrition of high-affinity B cells in chronic viral infection

GSE296780 Mus musculus Expression profiling by high throughput sequencing 8 samples Submitted 2026/03/17 Platform GPL19057
Summary
Perturbed B cell responses and late formation of neutralizing antibodies are hallmarks of chronic infections but the mechanisms underlying the dysfunctional humoral responses remain poorly defined. We used adoptive transfer of monoclonal anti-viral B cells (KL25) in the context of chronic lymphocytic choriomeningitis virus (LCMV) infection in mice and we observed late clonal deletion of the KL25 cells. This process was governed by the binding affinity of the KL25 B cell receptor (BCR) to its target, the viral glycoprotein (GP), and the persistence of the antigen. We found that the loss of the KL25 B cells was independent of IFN-I inflammation, and it was the result of Blimp-1-dependent differentiation. The late deletion of high-affinity B cells in chronic infection may explain the delayed neutralizing antibody response to persistent pathogens. Strategies to counter B cell clonal deletion should help us improve humoral immunity against chronic infectious diseases
Published in
Chronic infection perturbs the affinity hierarchy of antiviral B cells
Dimitrova M, Abreu-Mota T, Fixemer J et al. · Proceedings of the National Academy of Sciences of the United States of America 2026 · PMID 41915741 · doi:10.1073/pnas.2532422123
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Also filed as BioProject PRJNA1261038 and SRA study SRP584296. Searching any of these in the dataset finder brings you back here.

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