| First Author | Kamperschroer C | Year | 2008 |
| Journal | J Immunol | Volume | 181 |
| Issue | 6 | Pages | 3994-4003 |
| PubMed ID | 18768854 | Mgi Jnum | J:139100 |
| Mgi Id | MGI:3807322 | Doi | 10.4049/jimmunol.181.6.3994 |
| Citation | Kamperschroer C, et al. (2008) SAP enables T cells to help B cells by a mechanism distinct from Th cell programming or CD40 ligand regulation. J Immunol 181(6):3994-4003 |
| abstractText | 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. |
