| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Cambier, John Müller, Jennifer Gutierrez, Toni Mayeux, Jessica Nitschke, Lars Rickert, Robert Tedder, Thomas Garrett-Sinha, Lee Ann Luo, Wei Getahun, Andrew Parnes, Jane Satterthwaite, Anne B. Russell, Lisa |
| Description |
Author Affiliation: Luo W ( Department of Biochemistry, Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo, Buffalo, NY 14203); Mayeux J ( Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390); Gutierrez T ( Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390); Russell L ( Department of Biochemistry, Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo, Buffalo, NY 14203); Getahun A ( Department of Immunology, University of Colorado School of Medicine, Aurora, CO 90045); Müller J ( Division of Genetics, Department of Biology, University of Erlangen, 91058 Erlangen, Germany); Tedder T ( Department of Immunology, Duke University Medical Center, Durham, NC 27710); Parnes J ( Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305); Rickert R ( Program on Inflammatory Diseases, Infectious and Inflammatory Diseases Center, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037.); Nitschke L ( Division of Genetics, Department of Biology, University of Erlangen, 91058 Erlangen, Germany); Cambier J ( Department of Immunology, University of Colorado School of Medicine, Aurora, CO 90045); Satterthwaite AB ( Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390); Garrett-Sinha LA ( Department of Biochemistry, Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo, Buffalo, NY 14203) |
| Abstract |
Signaling through the BCR can drive B cell activation and contribute to B cell differentiation into Ab-secreting plasma cells. The positive BCR signal is counterbalanced by a number of membrane-localized inhibitory receptors that limit B cell activation and plasma cell differentiation. Deficiencies in these negative signaling pathways may cause autoantibody generation and autoimmune disease in both animal models and human patients. We have previously shown that the transcription factor Ets1 can restrain B cell differentiation into plasma cells. In this study, we tested the roles of the BCR and inhibitory receptors in controlling the expression of Ets1 in mouse B cells. We found that Ets1 is downregulated in B cells by BCR or TLR signaling through a pathway dependent on PI3K, Btk, IKK2, and JNK. Deficiencies in inhibitory pathways, such as a loss of the tyrosine kinase Lyn, the phosphatase Src homology region 2 domain-containing phosphatase 1 (SHP1) or membrane receptors CD22 and/or Siglec-G, result in enhanced BCR signaling and decreased Ets1 expression. Restoring Ets1 expression in Lyn- or SHP1-deficient B cells inhibits their enhanced plasma cell differentiation. Our findings indicate that downregulation of Ets1 occurs in response to B cell activation via either BCR or TLR signaling, thereby allowing B cell differentiation and that the maintenance of Ets1 expression is an important function of the inhibitory Lyn â CD22/SiglecG â SHP1 pathway in B cells. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| DOI |
10.4049/jimmunol.1400666 |
| Journal |
The Journal of Immunology |
| Issue Number |
2 |
| Volume Number |
193 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2014-07-15 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Cell Differentiation Immunology Plasma Cells Proto-oncogene Protein C-ets-1 Receptors, Antigen, B-cell Signal Transduction Animals B-lymphocytes Metabolism Blotting, Western Genetics Cell Line, Tumor Gene Expression Lectins Deficiency Mice Mice, 129 Strain Mice, Inbred C57bl Mice, Knockout Mice, Transgenic Phosphatidylinositol 3-kinases Phosphorylation Protein Tyrosine Phosphatase, Non-receptor Type 6 Protein-tyrosine Kinases Receptors, Cell Surface Reverse Transcriptase Polymerase Chain Reaction Sialic Acid Binding Ig-like Lectin 2 Src-family Kinases Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
