B cell and BAFF dependence of IFN-α-exaggerated disease in systemic lupus erythematosus-prone NZM 2328 mice

Noam Jacob, Shunhua Guo, Alexis Mathian, Michael N. Koss, Simona Gindea, Chaim Putterman, Chaim O. Jacob, William Stohl

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Abstract

IFN-α is a potent activator of innate and adaptive immunity, and its administration to preautoimmune (NZB × NZW)F1 mice promotes virulent systemic lupus erythematosus (SLE) disease. Given the known contributions of B cells and BAFF to SLE, we evaluated the ability of IFN-α administration to induce disease in wild-type (WT), B cell-deficient, and BAFF-deficient NZM 2328 mice. Whereas WT mice rapidly developed proliferative glomerulonephritis, marked proteinuria, and increased mortality in response to IFN-α administration, B cell-deficient mice developed neither renal pathology nor clinical disease. Moreover, BAFF-deficient mice, despite developing limited glomerular IgG and C3 deposition, also remained free of histological glomerulonephritis and clinical disease. Strikingly, similar T cell expansion and serum IgG responses were observed in adenovirus (Adv)-IFN-treated WT and BAFF-deficient mice despite their disparate pathological and clinical responses, whereas numbers of activated B cells increased in WT mice but not in BAFF-deficient mice. Nonetheless, B cell, plasma cell, and T cell infiltration of the kidneys in Adv-IFN-treated WT mice was similar to that in WT mice treated with Adv-control. Its ability to promote SLE disease in WT mice notwithstanding, IFN-α administration failed to drive the preferential expansion of CD4+ memory T cells that occurs during the natural course of disease, and glomerular infiltration of macrophages failed to associate with development of disease. These results collectively suggest that therapeutic targeting in SLE of BAFF and/or B cells in SLE could be successful even in states of IFN-α overexpression. Moreover, our results document important biological differences between IFN-α-driven and spontaneous natural SLE disease.

Original languageEnglish (US)
Pages (from-to)4984-4993
Number of pages10
JournalJournal of Immunology
Volume186
Issue number8
DOIs
StatePublished - Apr 15 2011

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Systemic Lupus Erythematosus
B-Lymphocytes
Adenoviridae
Glomerulonephritis
T-Lymphocytes
Immunoglobulin G
Kidney
Clinical Pathology
Adaptive Immunity
Plasma Cells
Proteinuria
Innate Immunity
Macrophages
Mortality

ASJC Scopus subject areas

  • Immunology

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B cell and BAFF dependence of IFN-α-exaggerated disease in systemic lupus erythematosus-prone NZM 2328 mice. / Jacob, Noam; Guo, Shunhua; Mathian, Alexis; Koss, Michael N.; Gindea, Simona; Putterman, Chaim; Jacob, Chaim O.; Stohl, William.

In: Journal of Immunology, Vol. 186, No. 8, 15.04.2011, p. 4984-4993.

Research output: Contribution to journalArticle

Jacob, Noam ; Guo, Shunhua ; Mathian, Alexis ; Koss, Michael N. ; Gindea, Simona ; Putterman, Chaim ; Jacob, Chaim O. ; Stohl, William. / B cell and BAFF dependence of IFN-α-exaggerated disease in systemic lupus erythematosus-prone NZM 2328 mice. In: Journal of Immunology. 2011 ; Vol. 186, No. 8. pp. 4984-4993.
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