Activation induced differential regulation of stem cell antigen-1 (Ly-6A/E) expression in murine B cells |
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Authors: | Chen Hui-Chen Frissora Frank Durbin Joan E Muthusamy Natarajan |
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Affiliation: | a Department of Pediatrics, Center for Human and Molecular Genetics, Columbus Children’s Research Institute, The Ohio State University, Columbus, OH 43205 USA b Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH 43205 USA c Department of Veterinary BioSciences, The Ohio State University, Columbus, OH 43205 USA d Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43205 USA |
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Abstract: | Expression of stem cell antigen-1 (Ly-6A/E) is developmentally regulated in murine B cells. However, little is known about its modulation during B cell activation. We report here the differential regulation of Ly-6A/E expression in response to diverse activation signals in mature B cells. Stimulation of resting B cells through the antigen receptor (BCR) inhibited, Ly-6A/E surface expression in dose dependent manner. Activation induced downregulation of Ly-6A/E is specific to BCR mediated signaling events as stimulation of B cells with anti-CD40, lipopolysaccharide or interferon-γ induced upregulation of Ly-6A/E surface expression. The activation induced differential modulation of Ly-6A/E expression is mediated at the mRNA levels. A role for BCR signaling in inhibition of Ly-6A/E expression was further confirmed using STAT-1−/− B cells, which expressed constitutive, but not inducible Ly-6A/E. The BCR induced inhibition of Ly-6A/E RNA and surface expression was mimicked by ionomycin, but not phorbol myristate acetate, indicating a role for calcium but not protein kinase C dependent signaling events. Inhibition of calcineurin reversed the BCR or ionomycin inhibited Ly-6A/E expression. Interestingly, in vitro differentiation analysis of Ly-6A/E+ and Ly-6A/E− splenic B cells revealed the Ly-6A/E+ cells to be the major source of antibody production, suggesting a potential role for Ly-6A/E in B cell differentiation. These studies provide the first evidence for activation induced differential modulation and differentiation of Ly-6A/E+ B cells. |
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Keywords: | B cells Stem cell antigen-1 Ly-6A E regulation Activation Differentiation |
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