Regulation of dendritic cell trafficking by the ADP-ribosyl cyclase CD38: impact on the development of humoral immunity.
Mice lacking CD38, an ectoenzyme that generates the calcium-mobilizing metabolite cADPR, make reduced T cell-dependent antibody responses. Despite the predicted role for CD38 in B cell activation, we find that CD38 regulates the migration of dendritic cell (DC) precursors from the blood to peripheral sites and controls the migration of mature DCs from sites of inflammation to lymph nodes. Thus, T cells are inefficiently primed in Cd38(-/-) mice, leading to poor humoral immune responses. We also show that CD38 and cADPR modulate calcium mobilization in chemokine-stimulated DCs and are required for the chemotaxis of immature and mature DCs to CCL2, CCL19, CCL21, and CXCL12. Therefore, CD38 regulates adaptive immunity by controlling chemokine receptor signaling in DCs.
Partida-Sánchez
Santiago
S
Trudeau Institute, 154 Algonquin Avenue, Saranac Lake, NY 12983, USA.
Goodrich
Stephen
S
Kusser
Kim
K
Oppenheimer
Norman
N
Randall
Troy D
TD
Lund
Frances E
FE
D036541:ADP-ribosyl Cyclase / Q000235:genetics / Q000502:physiology*; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D000917:Antibody Formation; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D002454:Cell Differentiation; D002633:Chemotaxis; D003713:Dendritic Cells / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D007295:Inositol Phosphates / Q000502:physiology; D008198:Lymph Nodes / Q000276:immunology; D008211:Lymphocyte Cooperation; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019707:Receptors, Chemokine / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D007295:Inositol Phosphates; D008562:Membrane Glycoproteins; D019707:Receptors, Chemokine; C092449:inositol 1,2,3-trisphosphate; D036541:ADP-ribosyl Cyclase; C498155:Cd38 protein, mouse; D051997:ADP-ribosyl Cyclase 1