Activation induced differential regulation of stem cell antigen-1 (Ly-6A/E) expression in murine B cells.
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-gamma 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.
Chen
Hui-Chen
HC
Department of Pediatrics, Center for Human and Molecular Genetics, Columbus Children's Research Institute, The Ohio State University, Columbus, OH 43205, USA.
Frissora
Frank
F
Durbin
Joan E
JE
Muthusamy
Natarajan
N
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000950:Antigens, Ly / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000950:Antigens, Ly; D019013:CD40 Antigens; D004268:DNA-Binding Proteins; D007476:Ionophores; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; C044203:anti-IgM; D015759:Ionomycin; D007371:Interferon-gamma; D011493:Protein Kinase C