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

Murillo Silva, Thao H. Nguyen, Phaethon Philbrook, Matthew Chu, Olivia Sears, Stephen Hatfield, Robert K. Abbott, Garnett Kelsoe, Michail V. Sitkovsky

Research output: Contribution to journalArticlepeer-review


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. Interclonal competition inhibits full participation of subdominant B cells in the germinal center (GC). Silva et al. demonstrate that selective elimination of immunodominant B cells during an active GC response allows subdominant B cells to expand unimpeded. Without competition, these subdominant cells generate an improved long-lived humoral response.

Original languageEnglish (US)
Pages (from-to)3672-3680
Number of pages9
JournalCell Reports
Issue number13
StatePublished - Dec 26 2017
Externally publishedYes


  • B cell selection
  • B cells
  • germinal center
  • immunodominance
  • immunoglobulin
  • interclonal competition
  • soluble antigen
  • subdominant
  • vaccine

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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