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Targeted Elimination of Immunodominant B Cells Drives the Germinal Center Reaction toward Subdominant Epitopes.

Publication ,  Journal Article
Silva, M; Nguyen, TH; Philbrook, P; Chu, M; Sears, O; Hatfield, S; Abbott, RK; Kelsoe, G; Sitkovsky, MV
Published in: Cell Rep
December 26, 2017

Rapidly evolving pathogens such as HIV or influenza can quickly mutate their antigenic profiles, reducing the efficacy of conventional vaccines. Despite this challenge, functionally required epitopes are highly conserved among heterologous viral strains and represent a key vulnerability that could be targeted during vaccine development. As the antigenicity of these conserved epitopes is frequently subdominant, there is a critical need for innovative vaccination strategies designed to target these neutralizing epitopes. Here, we immunized mice with antigens containing discrete immunodominant and subdominant moieties and show that treatment with soluble heterologous antigen bearing only the immunodominant epitope selectively suppresses these germinal center (GC) B cells. By exploiting this intrinsic tolerance mechanism, we promote the expansion of subdominant B cells in the GC and the subsequent long-lived components of the humoral response. We propose that this strategy may be applied to elicit preferential expansion of subdominant B cells that recognize weakly immunogenic epitopes on microbial pathogens.

Duke Scholars

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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

December 26, 2017

Volume

21

Issue

13

Start / End Page

3672 / 3680

Location

United States

Related Subject Headings

  • Solubility
  • Plasma Cells
  • Phenylacetates
  • Ovalbumin
  • Nitrophenols
  • Mice, Inbred C57BL
  • Immunodominant Epitopes
  • Germinal Center
  • Clone Cells
  • Cell Count
 

Citation

APA
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MLA
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Silva, M., Nguyen, T. H., Philbrook, P., Chu, M., Sears, O., Hatfield, S., … Sitkovsky, M. V. (2017). Targeted Elimination of Immunodominant B Cells Drives the Germinal Center Reaction toward Subdominant Epitopes. Cell Rep, 21(13), 3672–3680. https://doi.org/10.1016/j.celrep.2017.12.014
Silva, Murillo, Thao H. Nguyen, Phaethon Philbrook, Matthew Chu, Olivia Sears, Stephen Hatfield, Robert K. Abbott, Garnett Kelsoe, and Michail V. Sitkovsky. “Targeted Elimination of Immunodominant B Cells Drives the Germinal Center Reaction toward Subdominant Epitopes.Cell Rep 21, no. 13 (December 26, 2017): 3672–80. https://doi.org/10.1016/j.celrep.2017.12.014.
Silva M, Nguyen TH, Philbrook P, Chu M, Sears O, Hatfield S, et al. Targeted Elimination of Immunodominant B Cells Drives the Germinal Center Reaction toward Subdominant Epitopes. Cell Rep. 2017 Dec 26;21(13):3672–80.
Silva, Murillo, et al. “Targeted Elimination of Immunodominant B Cells Drives the Germinal Center Reaction toward Subdominant Epitopes.Cell Rep, vol. 21, no. 13, Dec. 2017, pp. 3672–80. Pubmed, doi:10.1016/j.celrep.2017.12.014.
Silva M, Nguyen TH, Philbrook P, Chu M, Sears O, Hatfield S, Abbott RK, Kelsoe G, Sitkovsky MV. Targeted Elimination of Immunodominant B Cells Drives the Germinal Center Reaction toward Subdominant Epitopes. Cell Rep. 2017 Dec 26;21(13):3672–3680.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

December 26, 2017

Volume

21

Issue

13

Start / End Page

3672 / 3680

Location

United States

Related Subject Headings

  • Solubility
  • Plasma Cells
  • Phenylacetates
  • Ovalbumin
  • Nitrophenols
  • Mice, Inbred C57BL
  • Immunodominant Epitopes
  • Germinal Center
  • Clone Cells
  • Cell Count