Cell Reports
Volume 25, Issue 2, 9 October 2018, Pages 321-327.e3
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Report
B Cell Competition for Restricted T Cell Help Suppresses Rare-Epitope Responses

https://doi.org/10.1016/j.celrep.2018.09.029Get rights and content
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Highlights

  • Naive B cells compete for antigen-restricted T cell help

  • Relative access to antigen determines clonal inclusion in humoral response

  • Quantity of CD4+ T cell helps directly modulate B cell clonal restriction

Summary

The immune system responds preferentially to particular antigenic-epitopes contained within complex immunogens, such as proteins or microbes. This poorly understood phenomenon, termed “immunodominance,” remains an obstacle to achieving polyvalent immune responses against multiple antigenic-epitopes through vaccination. We observed profound suppression in the hapten-specific antibody response in mice immunized with hapten-protein conjugate, mixed with an excess of protein, relative to that in mice immunized with hapten-protein alone. The suppression was robust (100-fold and 10-fold with a 10- or 2-fold excess of protein, respectively), stable over a 6-log range in antigen dose, observed within 10 days of vaccination, and resistant to boosting and adjuvants. Furthermore, there were reduced frequencies of antigen-specific germinal-center B cells and long-lived bone-marrow plasma cells. The mechanism of this “antigen-competition” was mediated largely by early access to T-helper cells. These results offer mechanistic insights into B cell competition during an immune response and suggest vaccination strategies against HIV, influenza, and dengue.

Keywords

Vaccination
humoral
immune
B cell
germinal center
antigen competition

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