Green Light for Dendritic Cell Movement

Science's STKE  23 Mar 2004:
Vol. 2004, Issue 225, pp. tw104-TW104
DOI: 10.1126/stke.2252004TW104

CD38 is a transmembrane protein with extracellular enzymatic activity that can produce adenosine diphosphate ribose (ADPR) and cyclic ADPR (cADPR). Mice deficient in CD38, which is expressed in both hematopoetic and nonhematopoetic cells including 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 loss of CD38 on B cells, Partida-Sánchez et al. provide evidence that the defect is at the level of the dendritic cells, which in CD38—/— mice do not migrate effectively to lymph nodes after inflammatory challenge in the skin. CD38—/— B cells were capable of responding when transferred by bone marrow transplant to B cell-deficient mice with otherwise normal bone marrow. B cell responses require T cell priming, which involves an interaction between T cells and antigen-presenting cells (such as dendritic cells). T cells were not effectively primed in CD38—/— mice. Although dendritic cells from CD38—/— mice were capable of maturing, they did not migrate properly to the sites for T cell interaction (lymph nodes). CD38—/— dendritic cells had defective migration in transwell assays with various chemokine receptor ligands, despite having apparently normal expression of the chemokine receptors. Indeed, CD38—/— dendritic cells had diminished calcium signaling in response to chemokines. Responses of wild-type dendritic cells (calcium signals and migration in transwell assays) were blocked by antagonists of cADPR, inositol triphosphate, or 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. Höpken and Lipp provide commentary.

S. Partida-Sánchez, S. Goodrich, K. Kusser, N. Oppenheimer, T. D. Randall, F. E. Lund, Regulation of dendritic cell trafficking by the ADP-ribosyl cyclase CD38: Impact on the development of humoral immunity. Immunity 20, 279-291 (2004). [Online Journal]

U. E. Höpken, M. Lipp, All roads lead to Rome: Triggering dendritic cell migration. Immunity 20, 244-246 (2004). [Online Journal]