ASSIGNMENT

Assignment



Chapter #11

Dendritic cells (DCs) are specialized and the most potent antigen presenting cells (APCs) compared to B cells and monocytes with a unique ability to prime effective immune responses. They express higher levels of MHC class II and accessory molecules on their surface than other professional APCs [1 and 2]. DCs can internalize antigens by phagocytosis , macropinocytosis and receptor-mediated interactions for efficient processing and presentation. In addition, DCs can secrete large amounts of IL-12, a cytokine critical for T-B cell interactions and antibody production .

Extensive work in rodents and humans has demonstrated that the potent accessory properties of DCs depend on a process of maturation [10, 11, 12, 13, 14 and 15]. Proinflamatory stimuli such as TNF-a, IL-1 and LPS induce DC maturation as well as upregulate the expression of adhesion and costimulatory molecules . Immature DCs process efficiently protein antigens but are relatively poor at activating naïve T cells. In contrast, mature DCs lose the capacity to take up proteins efficiently but have an increased ability to present processed antigens to activate lymphocytes [11. C. Winzler, P. Rovere, M. Rescigno, F. Granucci, G. Penna, L. Adorini, V.S. Zimmermann, J. Davoust and P. Ricciardi-Csatagnoli, Maturation stages of mouse dendritic cells in growth factor-dependent long-term cultures. J Exp Med 185 (1997), pp. 317-328. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (535)11 and 14]. DCs comprise three different subpopulations: two in the myeloid lineage, such as Langerhans cells and interstitial DCs, and one in the lymphoid lineage. Four subsets of DC precursors circulate in the peripheral blood: CD14+ monocytes, CD11c+ precursor DC, CD11c- precursor DC and a recently discovered natural interferon-producing cell precursor DC .

DCs can be obtained readily in sufficient quantities from BM and CD34+ blood progenitors [17, 18, 19, 20 and 21]. Human studies show that monocytes cultured in the presence of GM-CSF and IL-4 acquire many of the properties of DCs [22, 23, 24 and 25]. The generation of DCs from bovine blood monocytes has recently been described . The next important step in generating large numbers of DCs has been made by addition of Flt-3 ligand (Flt-3L), a tyrosine kinase receptor binding protein, to the cultures of BM and blood progenitor cells .

DCs, known for their T cell stimulatory properties, are now recognized to have major effects on B cell growth and Ig secretion [30, 31, 32, 33, 34, 35 and 36]. Some findings suggest that DCs may directly regulate B cell maturation through IL-12-dependent and IL-12-independent pathways . In vitro generated human DCs enhanced the proliferation of CD40-activated naïve or memory B cells in the absence of T cells and exogenous cytokines [34 and 35]. The mechanisms by which DCs induce B cell proliferation might involve CD40-independent release of soluble mediators different from IL-12 [31 and 33]. In the absence of exogenous cytokine, DCs strongly potentiate the differentiation of CD40-activated memory B cells toward IgG- and IgA-secreting cells (IL-12-independent pathway) [31 and ...