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. Specifically, murine WEHI-231 B lymphoma cells were exposed to environmentally relevant levels of Hg with or without concomitant BCR stimulation. The cellular phospho-proteomes were then profiled by LC-MS/MS. We found that for low-level exposures, Hg interference with signal transduction across the BCR pathway was predominantly associated with modification of phosphorylation of 12 phosphosites located on seven different proteins. Nine sites were serine, two sites tyrosine and one site threonine. Most of these sites are novel, in the sense that only the two tyrosine and one of the serine sites have previously been reported to be associated with BCR signaling.