MTOR promotes antiviral humoral immunity by differentially regulating CD4 helper T cell and B cell responses

Lilin Ye, Junghwa Lee, Lifan Xu, Ata Ur Rasheed Mohammed, Weiyan Li, J. Scott Hale, Wendy G. Tan, Tuoqi Wu, Carl W. Davis, Rafi Ahmed, Koichi Araki

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

mTOR has important roles in regulation of both innate and adaptive immunity, but whether and how mTOR modulates humoral immune responses have yet to be fully understood. To address this issue, we examined the effects of rapamycin, a specific inhibitor of mTOR, on B cell and CD4 T cell responses during acute infection with lymphocytic choriomeningitis virus. Rapamycin treatment resulted in suppression of virus-specific B cell responses by inhibiting proliferation of germinal center (GC) B cells. In contrast, the number of memory CD4 T cells was increased in rapamycin-treated mice. However, the drug treatment caused a striking bias of CD4 T cell differentiation into Th1 cells and substantially impaired formation of follicular helper T (Tfh) cells, which are essential for humoral immunity. Further experiments in which mTOR signaling was modulated by RNA interference (RNAi) revealed that B cells were the primary target cells of rapamycin for the impaired humoral immunity and that reduced Tfh formation in rapamycin-treated mice was due to lower GC B cell responses that are essential for Tfh generation. Additionally, we found that rapamycin had minimal effects on B cell responses activated by lipopolysaccharide (LPS), which stimulates B cells in an antigen-independent manner, suggesting that rapamycin specifically inhibits B cell responses induced by B cell receptor stimulation with antigen. Together, these findings demonstrate that mTOR signals play an essential role in antigen-specific humoral immune responses by differentially regulating B cell and CD4 T cell responses during acute viral infection and that rapamycin treatment alters the interplay of immune cell subsets involved in antiviral humoral immunity.

Original languageEnglish (US)
Article numbere01653-16
JournalJournal of virology
Volume91
Issue number4
DOIs
StatePublished - 2017
Externally publishedYes

Keywords

  • B cell responses
  • CD4 T cells
  • Humoral immunity
  • Immunization
  • MTOR
  • Rapamycin
  • Th1/Tfh response
  • Viral immunity
  • Viral infection

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Fingerprint

Dive into the research topics of 'MTOR promotes antiviral humoral immunity by differentially regulating CD4 helper T cell and B cell responses'. Together they form a unique fingerprint.

Cite this