Naturally occurring autoimmune disease in (NZB X NZW) F1 mice is correlated with suppression of MZ B cell development due to aberrant B Cell Receptor (BCR) signaling, which is exacerbated by exposure to inorganic mercury.

Autoimmune diseases are multifactorial and include environmental as well as genetic drivers. Although much progress has been made in understanding the nature of genetic underpinnings of autoimmune disease, by comparison much less is understood regarding how environmental factors interact with genetics in the development of autoimmunity and autoimmune disease. In this report, we utilize the (NZB X NZW) F1 mouse model of Systemic Lupus Erythematosus (SLE).

Mercury intoxication disrupts tonic signaling in B cells, and may promote autoimmunity due to abnormal phosphorylation of STIM-1 and other autoimmunity risk associated phosphoproteins involved in BCR signaling.

Epidemiological studies link exposure to mercury with autoimmune disease. Unfortunately, in spite of considerable effort, no generally accepted mechanistic understanding of how mercury functions with respect to the etiology of autoimmune disease is currently available. Nevertheless, autoimmune disease often arises because of defective B cell signaling.

At low levels, inorganic mercury interference with antigen signaling is associated with modifications to a panel of novel phosphoserine sites in B cell receptor pathway proteins.

Epidemiological studies indicate that human and animal exposure to environmental mercury (Hg) disrupts normal immune system function, but the molecular mechanism responsible for this is still unresolved. We have previously utilized phospho-proteomic mass spectrometry to demonstrate that in the absence of B Cell Receptor (BCR) stimulation, exposure of B cells to Hg induces significant changes to a great many elements of the BCR signaling pathway in a concentration dependent manner. In this report, we have extended those initial findings by utilizing mass spectrometry to evaluate in detail the effect of low-level Hg exposure on BCR induced phospho-proteomic changes.