FcγRIIB deficiency leads to autoimmunity and a defective response to apoptosis in MrL-MpJ mice

Tracy L. McGaha, Mikael C I Karlsson, Jeffrey V. Ravetch

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Data suggests that modulation of FcγRIIB expression represents a significant risk factor for the development of autoimmunity. In this study, we investigated this notion in mice that possess genetics permissible for the development of autoimmunity. To this end, Mrl-MpJ Fcgr2b-/- mice were monitored for the development of autoreactivity. We found that FcγRIIB deficiency led to chronic B cell activation associated with increased germinal center and plasma cell accumulation in the spleen. Likewise, Mrl-MpJ Fcgr2b-/- mice exhibited significant serum IgG reactivity against DNA. We further analyzed the IgG isotype contribution to the anti-dsDNA response and found increases in all subtypes with the exception of IgG3. In particular, we found large increases in IgGl and IgG2b autoreactivity correlating with significant increases in immune complex deposition and kidney pathology. Finally, we found dendritic cells derived from Mrl-MpJ Fcgr2b-I- mice greatly increased IL-12 expression upon coincubation with apoptotic thymocytes compared with wild-type controls. The results indicate that FcyRIIB is an important regulator of peripheral tolerance and attenuation of the inhibitory signal it provides enhances autoimmune disease on susceptible backgrounds. Additionally, the data indicates FcγRIIB function has a significant impact on APC activity, suggesting a prominent role in dendritic cell activity in response to interaction with particulate autoantigens. The Journal of Immunology, 2008, 180: 5670-5679.

Original languageEnglish (US)
Pages (from-to)5670-5679
Number of pages10
JournalJournal of Immunology
Volume180
Issue number8
StatePublished - Apr 15 2008

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Autoimmunity
Apoptosis
Immunoglobulin G
Dendritic Cells
Peripheral Tolerance
Germinal Center
Autoantigens
Thymocytes
Interleukin-12
Plasma Cells
Allergy and Immunology
Antigen-Antibody Complex
Autoimmune Diseases
B-Lymphocytes
Spleen
Pathology
Kidney
DNA
Serum

ASJC Scopus subject areas

  • Immunology

Cite this

McGaha, T. L., Karlsson, M. C. I., & Ravetch, J. V. (2008). FcγRIIB deficiency leads to autoimmunity and a defective response to apoptosis in MrL-MpJ mice. Journal of Immunology, 180(8), 5670-5679.

FcγRIIB deficiency leads to autoimmunity and a defective response to apoptosis in MrL-MpJ mice. / McGaha, Tracy L.; Karlsson, Mikael C I; Ravetch, Jeffrey V.

In: Journal of Immunology, Vol. 180, No. 8, 15.04.2008, p. 5670-5679.

Research output: Contribution to journalArticle

McGaha, TL, Karlsson, MCI & Ravetch, JV 2008, 'FcγRIIB deficiency leads to autoimmunity and a defective response to apoptosis in MrL-MpJ mice', Journal of Immunology, vol. 180, no. 8, pp. 5670-5679.
McGaha, Tracy L. ; Karlsson, Mikael C I ; Ravetch, Jeffrey V. / FcγRIIB deficiency leads to autoimmunity and a defective response to apoptosis in MrL-MpJ mice. In: Journal of Immunology. 2008 ; Vol. 180, No. 8. pp. 5670-5679.
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