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Dermatology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892
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 IIhigh 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, 
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.
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