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Autoimmune Diseases
Volume 2014, Article ID 239358, 10 pages
http://dx.doi.org/10.1155/2014/239358
Research Article

Elements of the B Cell Signalosome Are Differentially Affected by Mercury Intoxication

1Department of Immunology and Microbiology, Wayne State University, Detroit, MI 48201, USA
2Department of Environmental Medicine, University of Rochester, Rochester, NY 14642, USA

Received 1 October 2013; Revised 7 January 2014; Accepted 20 January 2014; Published 4 May 2014

Academic Editor: K. Michael Pollard

Copyright © 2014 Randall F. Gill et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

It has been suggested that environmental exposures to mercury contribute to autoimmune disease. Disruption of BCR signaling is associated with failure of central tolerance and autoimmunity, and we have previously shown that low levels of Hg2+ interfere with BCR signaling. In this report we have employed multiparametric phosphoflow cytometry, as well as a novel generalization of the Overton algorithm from one- to two-dimensional unimodal distributions to simultaneously monitor the effect of low level Hg2+ intoxication on activation of ERK and several upstream elements of the BCR signaling pathway in WEHI-231 B cells. We have found that, after exposure to low levels of Hg2+, only about a third of the cells are sensitive to the metal. For those cells which are sensitive, we confirm our earlier work that activation of ERK is attenuated but now report that Hg2+ has little upstream effect on the Btk tyrosine kinase. On the other hand, we find that signaling upstream through the Syk tyrosine kinase is actually augmented, as is upstream activation of the B cell signalosome scaffolding protein BLNK.