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

Autoimmunity

PubMedID: 22283427

McGaha TL, Ma Z, Ravishankar B, Gabunia K, McMenamin M, Madaio MP. Heterologous protein incites abnormal plasma cell accumulation and autoimmunity in MRL-MpJ mice. Autoimmunity. 2012;45(4):279-89.
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.