SOCS3 Deletion in B Cells Alters Cytokine Responses and Germinal Center Output
| Autor: | Lorraine Robb, Christine A White, Sarah Jones, David M. Tarlinton, Warren S. Alexander |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_treatment
Cellular differentiation Immunology Naive B cell B-cell receptor B-Lymphocyte Subsets Bone Marrow Cells Mice Transgenic Suppressor of Cytokine Signaling Proteins Article Mice Cell Movement medicine Animals Immunology and Allergy Cells Cultured B cell Cell Proliferation Mice Knockout CD40 biology Precursor Cells B-Lymphoid digestive oral and skin physiology Gene Expression Regulation Developmental Germinal center Cell Differentiation Immunoglobulin E Germinal Center Molecular biology Mice Inbred C57BL B-1 cell Cytokine medicine.anatomical_structure Suppressor of Cytokine Signaling 3 Protein biology.protein Cytokines Binding Sites Antibody Gene Deletion |
| Zdroj: | The Journal of Immunology. 187:6318-6326 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1102057 |
| Popis: | B cell behavior is fine-tuned by internal regulatory mechanisms and external cues such as cytokines and chemokines. Suppressor of cytokine signaling 3 (SOCS3) is a key regulator of STAT3-dependent cytokine responses in many cell types and has been reported to inhibit CXCL12-induced retention of immature B cells in the bone marrow. Using mice with SOCS3 exclusively deleted in the B cell lineage (Socs3Δ/Δmb1cre+), we analyzed the role of SOCS3 in the response of these cells to CXCL12 and the STAT3-inducing cytokines IL-6 and IL-21. Our findings refute a B cell-intrinsic role for SOCS3 in B cell development, because SOCS3 deletion in the B lineage did not affect B cell populations in naive mice. SOCS3 was strongly induced in B cells stimulated with IL-21 and in plasma cells exposed to IL-6. Its deletion permitted excessive and prolonged STAT3 signaling following IL-6 stimulation of plasma cells and, in a T cell-dependent immunization model, reduced the number of germinal center B cells formed and altered the production of Ag-specific IgM and IgE. These data demonstrate a novel regulatory signal transduction circuit in plasma cells, providing, to our knowledge, the first evidence of how these long-lived, sessile cells respond to the external signals that mediate their longevity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|