CXCR5-transduced bone marrow-derived dendritic cells traffic to B cell zones of lymph nodes and modify antigen-specific immune responses.
Skin-derived migratory dendritic cells (DC), in contrast to bone marrow-derived DC (BMDC), express CXCR5, respond to the chemokine CXC ligand 13 (CXCL13) in vitro, and are capable of migrating to B cell zones (BCZ) in lymph nodes (LN) in vivo. Herein, we analyzed the surface phenotype of skin-derived migratory DC and found that 15-35% of MHC class II(high) cells showed high levels of expression of CXCR5 but expressed low levels of DEC205, a suggested characteristic of dermal-type DC in mice. To study the effects of CXCR5 on the trafficking dynamics of DC, we stably expressed CXCR5 in BMDC by retroviral gene transduction. CXCR5 was detected by flow cytometry on transduced cells, which responded to CXCL13 in vitro in chemotaxis assays (3-fold over nontransduced BMDC, p < 0.01). When injected into the footpads of mice, approximately 40% of injected CXCR5-BMDC were observed in BCZ of draining LN. Mice were vaccinated with CXCR5- and vector-BMDC that were pulsed with keyhole limpet hemocyanin (KLH) to induce Ag-specific cellular and humoral immune responses. Mice injected with CXCR5-BMDC (vs vector-BMDC) demonstrated marginally less footpad swelling in response to intradermal injection of KLH. Interestingly, significantly higher levels of KLH-specific IgG (p < 0.05) and IgM (p < 0.01) were found in the serum of mice injected with CXCR5-BMDC compared with mice immunized with vector-transduced BMDC. Thus, CXCR5 is predominantly expressed by dermal-type DC. Moreover, CXCR5 directs BMDC to BCZ of LN in vivo and modifies Ag-specific immune responses induced by BMDC vaccination.
Wu
Meng-Tse
MT
Dermatology Branch, Center for Cancer Research, National Cancer Institute, Building 10 Room 12N246, 10 Center Drive, Bethesda, MD 20892.
Hwang
Sam T
ST
D000818:Animals; D015703:Antigens, CD; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000494:pharmacology; D002633:Chemotaxis / Q000235:genetics / Q000276:immunology*; D046508:Culture Techniques; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D018985:Epitopes, B-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D037181:Lectins, C-Type; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D015778:Minor Histocompatibility Antigens; D054380:Receptors, CXCR5; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000235:genetics*; D012190:Retroviridae / Q000235:genetics; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014161:Transduction, Genetic / Q000379:methods
D015703:Antigens, CD; C513179:CXCR5 protein, mouse; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; C486386:Cxcl13 protein, mouse; C093569:DEC-205 receptor; D018985:Epitopes, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D015778:Minor Histocompatibility Antigens; D054380:Receptors, CXCR5; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine