Transfected human B cells: a new model to study the functional and immunostimulatory consequences of APP production.

The ubiquitously expressed Alzheimer amyloid precursor protein (APP) has raised wide interest in view of its connection with Alzheimer's disease. We now provide a novel extraneuronal cell model in which human Epstein-Barr virus transformed B cells that constitutively hardly produce APP are transfected with wild-type or mutated APP695, harboring the Swedish mutation APPsw, or a dilysine endoplasmic reticulum retrieval motif--APP(ER). This leads to the generation of three types of cells, one with a high secretion of soluble APPs but low levels of intracellular APP, another with a high intracellular APP retention but a low APP secretion, and a third in which APP maturation and secretion are strongly impaired. The suitability of our cell model for various purposes is proven by its usage in different systems. We demonstrate that it is a useful tool for studies on the physiology of APPs and represents a good model system to analyze the cellular mechanisms of Abeta-directed autoimmune reactivity.

Whole virus influenza vaccine activates dendritic cells (DC) and stimulates cytokine production by peripheral blood mononuclear cells (PBMC) while subunit vaccines support T cell proliferation.

Three types of trivalent influenza vaccines were analysed for their in vitro stimulatory properties on immune cells from young healthy volunteers. A whole inactivated virus (WV) vaccine, a conventional subunit (c-SU) preparation and a new virosomal subunit (v-SU) vaccine were used. Blood-derived DC up-regulated MHC class II, CD54, CD80 and CD86 after exposure to WV vaccine, indicating their functional maturation, but were only moderately affected by subunit (SU) vaccines. In addition, IL-12 and tumour necrosis factor-alpha (TNF-alpha) secretion by DC were markedly enhanced by WV, but not by SU vaccines. The production of IL-2 and interferon-gamma (IFN-gamma) by PBMC was also strongly stimulated by WV, but much less by SU vaccines, among which the v-SU vaccine was a better stimulator of IL-2 secretion. In contrast to WV vaccine both SU vaccines were powerful stimulators of PBMC proliferation. Our results suggest that the presence of influenza core components leads to the activation of DC and triggers the production of cytokines by PBMC. SU vaccines are in contrast excellent stimulators of T cell growth. A combination of WV and SU vaccines in immunization regimes might allow optimal T cell priming as well as the efficient generation and maintenance of memory cells.