SAP enables T cells to help B cells by a mechanism distinct from Th cell programming or CD40 ligand regulation
| Autor: | Susan L. Swain, Yongqing Zhang, Cris Kamperschroer, Deborah M. Roberts, Nan-ping Weng |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cell signaling genetic structures Transgene T cell Cellular differentiation Immunology Cell CD40 Ligand Lymphocyte Cooperation B-Lymphocyte Subsets Mice Transgenic Cell Communication Article Mice medicine Immunology and Allergy Animals Signaling Lymphocytic Activation Molecule Associated Protein B cell Cells Cultured Mice Knockout CD40 biology Intracellular Signaling Peptides and Proteins Cell Differentiation T-Lymphocytes Helper-Inducer eye diseases Mice Mutant Strains Cell biology Mice Inbred C57BL medicine.anatomical_structure biology.protein Signal transduction Signal Transduction |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 181(6) |
| ISSN: | 1550-6606 |
| Popis: | Genetic mutations disrupting the function of signaling lymphocytic activation molecule-associated protein (SAP) lead to T cell intrinsic defects in T cell-dependent Ab responses. To better understand how SAP enables Th cells to help B cells, we first assessed whether molecules important for B cell help are dysregulated in SAP-deficient (SAP knockout (KO)) mice. CD40 ligand (CD40L) expression was enhanced on unpolarized SAP KO T cells; however, Th2 polarization returned their CD40L expression to wild-type levels without rescuing their ability to help B cells. CD40L also localized normally to the site of contact between SAP KO T cells and Ag-bearing B cells. Finally, CD40L-deficient Th cells and SAP KO Th cells differed in their abilities to help B cells in vitro. These data argue that Ab defects caused by SAP deficiency do not result from a loss of CD40L regulation or CD40L function on CD4 T cells. SAP KO Th cells additionally displayed normal patterns of migration and expression of ICOS and CXCR5. Global gene expression was remarkably similar in activated SAP KO vs wild-type T cells, prompting us to investigate whether SAP is necessary for “programming” T cells to become B cell helpers. By restricting SAP expression during differentiation, we determined that SAP is not required during the first 5 days of T cell activation/differentiation to generate Th cells capable of helping B cells. Instead, SAP is necessary for very late stages of differentiation or, most likely, for allowing Th cells to communicate during cognate T:B interactions. |
| Databáze: | OpenAIRE |
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