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Toxicol Appl Pharmacol. 2017 Sep 1;330:22-29. doi: 10.1016/j.taap.2017.06.022. Epub 2017 Jun 28.

Low level exposure to inorganic mercury interferes with B cell receptor signaling in transitional type 1 B cells.

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Department of Immunology, Microbiology and Biochemistry, Wayne State University, Detroit, MI, United States.
Department of Environmental Medicine, University of Rochester, Rochester, NY, United States.
Department of Immunology, Microbiology and Biochemistry, Wayne State University, Detroit, MI, United States; Center for Urban Responses to Environmental Stressors (CURES), Wayne State University, Detroit, MI, United States. Electronic address:


Mercury (Hg) has been implicated as a factor contributing to autoimmune disease in animal models and humans. However the mechanism by which this occurs has remained elusive. Since the discovery of B cells it has been appreciated by immunologists that during the normal course of B cell development, some immature B cells must be generated that produce immunoglobulin reactive to self-antigens (auto-antibodies). However in the course of normal development, the vast majority of immature auto-reactive B cells are prevented from maturing by processes collectively known as tolerance. Autoimmune disease arises when these mechanisms of tolerance are disrupted. In the B cell compartment, it is firmly established that tolerance depends in part upon negative selection of self-reactive immature (transitional type 1) B cells. In these cells negative selection depends upon signals generated by the B Cell Receptor (BCR), in the sense that those T1 B cells who's BCRs most strongly bind to, and so generate the strongest signals to self-antigens are neutralized. In this report we have utilized multicolor phosphoflow cytometry to show that in immature T1 B cells Hg attenuates signal generation by the BCR through mechanisms that may involve Lyn, a key tyrosine kinase in the BCR signal transduction pathway. We suggest that exposure to low, environmentally relevant levels of Hg, disrupts tolerance by interfering with BCR signaling in immature B cells, potentially leading to the appearance of mature auto-reactive B cells which have the ability to contribute to auto-immune disease.


Autoimmunity; B cell receptor (BCR); Mercury; Transitional type 1 (T1) B cell

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