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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Kang, S; Rogers, JL; Monteith, AJ; Jiang, C; Schmitz, J; Clarke, SH; Tarrant, TK; Truong, YK; Diaz, M; Fedoriw, Y; Vilen, BJ

Published Date

  • May 15, 2016

Published In

Volume / Issue

  • 196 / 10

Start / End Page

  • 4030 - 4039

PubMed ID

  • 27059595

Pubmed Central ID

  • PMC4868781

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1500418


  • eng

Conference Location

  • United States