Apoptotic Debris Accumulates on Hematopoietic Cells and Promotes Disease in Murine and Human Systemic Lupus Erythematosus

J Immunol. 2016 May 15;196(10):4030-9. doi: 10.4049/jimmunol.1500418. Epub 2016 Apr 8.


Apoptotic debris, autoantibody, and IgG-immune complexes (ICs) have long been implicated in the inflammation associated with systemic lupus erythematosus (SLE); however, it remains unclear whether they initiate immune-mediated events that promote disease. In this study, we show that PBMCs from SLE patients experiencing active disease, and hematopoietic cells from lupus-prone MRL/lpr and NZM2410 mice accumulate markedly elevated levels of surface-bound nuclear self-antigens. On dendritic cells (DCs) and macrophages (MFs), the self-antigens are part of IgG-ICs that promote FcγRI-mediated signal transduction. Accumulation of IgG-ICs is evident on ex vivo myeloid cells from MRL/lpr mice by 10 wk of age and steadily increases prior to lupus nephritis. IgG and FcγRI play a critical role in disease pathology. Passive transfer of pathogenic IgG into IgG-deficient MRL/lpr mice promotes the accumulation of IgG-ICs prior to significant B cell expansion, BAFF secretion, and lupus nephritis. In contrast, diminishing the burden IgG-ICs in MRL/lpr mice through deficiency in FcγRI markedly improves these lupus pathologies. Taken together, our findings reveal a previously unappreciated role for the cell surface accumulation of IgG-ICs in human and murine lupus.

Publication types

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

MeSH terms

  • Adult
  • Animals
  • Apoptosis*
  • Autoantigens / immunology
  • Autoantigens / metabolism
  • B-Cell Activating Factor / metabolism
  • Blood Cells / immunology*
  • Dendritic Cells / immunology*
  • Female
  • Humans
  • Lupus Erythematosus, Systemic / immunology*
  • Macrophages / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred MRL lpr
  • Mice, Knockout
  • Middle Aged
  • Receptors, IgG / genetics
  • Young Adult


  • Autoantigens
  • B-Cell Activating Factor
  • Fcgr1 protein, mouse
  • Fcgr3 protein, mouse
  • Receptors, IgG
  • Tnfsf13b protein, mouse