A Pathogenic Role for Splenic B1 Cells in SIV Disease Progression in Rhesus Macaques

Front Immunol. 2019 Mar 19;10:511. doi: 10.3389/fimmu.2019.00511. eCollection 2019.

Abstract

B1 cells spontaneously produce protective natural antibodies which provide the first line of defense against a variety of pathogens. Although these natural antibodies share similar autoreactive features with several HIV-1 broadly neutralizing antibodies, the role of B1 cells in HIV/SIV disease progression is unknown. We report the presence of human-like B1 cells in rhesus macaques. During chronic SIV infection, we found that the frequency of splenic CD11b+ B1 cells positively correlated with plasma SIV viral load and exhausted T cells. Mechanistically, we discovered that splenic CD11b+ B1 cells express PD-L2 and IL-10, and were able to induce PD-1 upregulation on CD4+ T cells in vitro. These findings suggest that splenic CD11b+ B1 cells may contribute to the regulation of SIV plasma viral load by enhancing T cell exhaustion. Therefore, understanding the mechanisms that govern their function in rhesus macaques may lead to novel therapeutic strategies for impeding HIV/SIV disease progression.

Keywords: B1 cells; T cells; exhaustion; rhesus macaque; simian immunodeficiency virus.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • B-Lymphocyte Subsets / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • Disease Progression
  • Female
  • Macaca mulatta
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Immunodeficiency Virus / immunology*
  • Spleen / immunology*
  • Viral Load / methods