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Dendritic Cells and Monocyte/Macrophages That Create the IL-6/APRIL-Rich Lymph Node Microenvironments Where Plasmablasts Mature¹

Elodie Mohr^2,*, Karine Serre^*, Rudolf A. Manz, Adam F. Cunningham^*, Mahmood Khan^*, Deborah L. Hardie^*, Roger Bird^* and Ian C. M. MacLennan^*

^* Medical Research Council Centre for Immune Regulation, University of Birmingham Medical School, Birmingham, United Kingdom; and Department for Humoral Immunology, German Arthritis Research Centre, Berlin, Germany

IL-6 and APRIL influence the growth, differentiation, and survival of normal and neoplastic Ab-forming cells (AFC). In this study, we identify two subsets of myeloid cells that associate with the AFC and are the main producers of these factors during a T-dependent Ab response to alum-precipitated protein in mouse lymph nodes. First CD11c⁺CD8^– dendritic cells located in the perivascular area of the T zone provide about half of the IL-6 mRNA produced in the node together with significant amounts of APRIL mRNA. The number of these cells increases during the response, at least in part due to local proliferation. The second subset comprises Gr1⁺CD11b⁺F4/80⁺ monocyte/macrophages. These colonize the medullary cords during the response and are the other main IL-6 mRNA producers and the greatest source of APRIL mRNA. This medullary cord monocyte/macrophage subset results in local increase of APRIL mRNA that mirrors the polarity of CXCL12 expression in the node. The distribution of these myeloid cell subsets correlates with a gradient of AFC maturation assessed by progressive loss of Ki67 as AFC pass from the B cell follicle along the perivascular areas to the medullary cords.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was funded by a programme grant from the British Medical Research Council. R.A.M. is supported by a Deutsche Forschungsgemeinschaft Grant MA 2273/4-2.

² Address correspondence and reprint requests to Dr. Elodie Mohr, Medical Research Council Centre for Immune Regulation, Room 435, Institute of Biomedical Research building, University of Birmingham Medical School, Vincent Drive, Birmingham B15 2TT, U.K. E-mail address: e.mohr{at}bham.ac.uk

³ Abbreviations used in this paper: LN, lymph node; AFC, Ab-forming cell; DC, dendritic cell; BAFF, B cell-activating factor; GC, germinal center; APRIL, a proliferation-inducing ligand; alumNP-OVA, aluminum hydroxide-precipitated (4-hydroxy-3-nitrophenyl) acetyl ovalbumin.

⁴ The online version of this article contains supplemental material.

This article has been cited by other articles:

				E. Belnoue, T. Matthes, C.-A. Siegrist, and B. Huard Comment on "Dendritic Cells and Monocyte/Macrophages That Create the IL-6/APRIL-Rich Lymph Node Microenvironment Where Plasmablasts Mature" J. Immunol., May 1, 2009; 182(9): 5159 - 5159. [Full Text] [PDF]

				E. Mohr, K. Serre, and I. MacLennan Response to the Comments on "Dendritic Cells and Monocyte/Macrophages That Create the IL-6/APRIL-Rich Lymph Node Microenvironment Where Plasmablasts Mature" J. Immunol., May 1, 2009; 182(9): 5160 - 5160. [Full Text] [PDF]