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In Support of Dendritic Cell Migration

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Science  02 Apr 2004:
Vol. 304, Issue 5667, pp. 19
DOI: 10.1126/science.304.5667.19b

CD38 is a transmembrane protein with extracellular enzymatic activity that can produce adenosine diphosphate ribose (ADPR) and cyclic ADPR (cADPR). Mice deficient for CD38, which is expressed in both B cells and dendritic cells, are unable to mount an effective T cell-dependent antibody response. Although this was initially suggested to be due to the absence of CD38 on B cells, Partida-Sánchez et al. show that CD38−/− B cells were capable of responding when transferred by bone marrow transplant to B cell-deficient mice with otherwise normal bone marrow. The B cell response requires T cell priming, which relies on an interaction between T cells and antigen-presenting cells (such as dendritic cells). Although dendritic cells from CD38−/− mice were capable of maturing, they did not migrate properly to the sites for T cell interaction (lymph nodes). In vitro, CD38−/− dendritic cells displayed defective migration and diminished calcium signaling in response to chemokines, despite having apparently normal expression of the chemokine receptors, and responses in wild-type dendritic cells were blocked by antagonists of cADPR and inositol triphosphate or by chelation of extracellular calcium. Thus, the authors suggest that CD38 enhances calcium mobilization in response to chemokine receptor activation through activation of plasma membrane calcium channels. — NG

Immunity 20, 279 (2004).

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