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Author Notes:

Correspondence: bpulend@stanford.edu

AUTHOR CONTRIBUTIONS: Conceptualization, M.C.W. and B.P.; Methodology, M.C.W. and B.P.; Formal Analysis, M.C.W.; Investigation, M.C.W., E.H.K., and W.L.; Writing – Original Draft, M.C.W.; Writing – Review & Editing, B.P.; Visualization, M.C.W.; Super-vision, B.P.; Funding Acquisition, M.C.W. and B.P.

We acknowledge Dr. Florian Krammer for providing materials critical to portions of this project but ultimately not included in the manuscript.

We also thank members of the Pulendran lab, including C. Sinclair, M. Johnson, and R. Ravindran for critical insights in project design and execution.

The authors declare no competing interests.

Subject:

Research Funding:

We acknowledge funding from the NIH (R37 DK057665, R37 AI048638, U19 AI090023, T32 DK07656, and U19 AI057266 to B.P.), the Bill and Melinda Gates Foundation, and Action Cycling Atlanta (to M.C.W.) for supporting this work through grants and fellowships.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell Biology
  • GERMINAL-CENTERS
  • INNATE IMMUNITY
  • AFFINITY MATURATION
  • CLONAL SELECTION
  • VACCINES
  • MEMORY

B Cell Competition for Restricted T Cell Help Suppresses Rare-Epitope Responses

Tools:

Journal Title:

Cell Reports

Volume:

Volume 25, Number 2

Publisher:

, Pages 321-+

Type of Work:

Article | Final Publisher PDF

Abstract:

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. Vaccination success depends on the immune system's ability to produce antibodies against highly specific pathogen targets, but the rules for how targets are selected remains poorly understood. Woodruff et al. describe a competition for resources among antibody producers that selects the cells, and thus targets, of the ensuing response.

Copyright information:

© 2018 The Author(s)

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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