Heterologous protein incites abnormal plasma cell accumulation and autoimmunity in MRL-MpJ mice

Tracy L. McGaha, Zhongjie Ma, Buvana Ravishankar, Khatuna Gabunia, Malgorzata McMenamin, Michael P. Madaio

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Although it is evident that there is complex interplay among genetic and environmental factors contributing to systemic autoimmunity, the events inciting autoreactivity are incompletely understood. Previously we demonstrated that MRL-MpJ mice posses a genetic background susceptible to autoimmunity development under conditions of altered inhibitory signaling. To gain better understanding of the influence of exogenous factors on autoreactivity in susceptible individuals, young MRL-MpJ mice were challenged with a single injection of heterologous protein and evaluated for evidence of autoimmunity. We found that MRL-MpJ mice developed high titer serum reactivity to DNA within 1 week of protein administration reaching maximal levels within 1 month. Importantly, the level of autoimmunity was sustained for an extended period of time (6 months). This was accompanied by a substantial increase in germinal center B cell and plasma cell numbers. In contrast, control mice showed no change in autoreactivity or lymphocyte homeostasis. Autoimmunity was dependent on marginal zone B cells as their depletion reduced serum auto-reactivity after challenge, thus suggesting immune stimulation with heterologous proteins can precipitate loss of B cell tolerance and autoimmunity in genetically prone individuals. This model may provide an important tool to further investigate the mechanisms whereby environmental stimuli trigger autoimmune reactivity in susceptible hosts.

Original languageEnglish (US)
Pages (from-to)279-289
Number of pages11
JournalAutoimmunity
Volume45
Issue number4
DOIs
StatePublished - Jun 1 2012

Keywords

  • MRL-MpJ mice
  • Marginal zone B cell
  • autoantibody
  • systemic lupus erythematosus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    McGaha, T. L., Ma, Z., Ravishankar, B., Gabunia, K., McMenamin, M., & Madaio, M. P. (2012). Heterologous protein incites abnormal plasma cell accumulation and autoimmunity in MRL-MpJ mice. Autoimmunity, 45(4), 279-289. https://doi.org/10.3109/08916934.2012.654864