title: SAP enables T cells to help B cells by a mechanism distinct from Th cell programming or CD40 ligand regulation.
abstract: 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.
authors.affiliation: Trudeau Institute, Saranac Lake, NY 12983, USA.
authors.forename: Cris
authors.initials: C
authors.lastname: Kamperschroer
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Roberts
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Zhang
authors.forename: Nan-Ping
authors.initials: NP
authors.lastname: Weng
authors.forename: Susan L
authors.initials: SL
authors.lastname: Swain