Activated Murine B Lymphocytes and Dendritic Cells Produce a Novel CC Chemokine which Acts Selectively on Activated T Cells

doi:10.1084/jem.188.3.451

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J. Exp. Med., Volume 188, Number 3, August 3, 1998 451-463

Activated Murine B Lymphocytes and Dendritic Cells Produce a Novel CC Chemokine which Acts Selectively on Activated T Cells

By Christoph Schaniel,^* Evangelia Pardali, Federica Sallusto,^* Mattheos Speletas, Christiane Ruedl,^* Takeyuki Shimizu,^* Thomas Seidl,^* Jan Andersson,^* Fritz Melchers,^* Antonius G. Rolink,^* and Paschalis Sideras^*

From the ^* Basel Institute for Immunology, CH-4005, Basel, Switzerland; and the Department of Applied Cell and Molecular Biology, Division of Tumour Biology, Umeå University, 901 87 Umeå, Sweden

Genes were isolated using the suppression subtractive hybridization method by stimulation of pro/pre B cells with anti-CD40and interleukin (IL)-4 to mature Sµ-S $epsilon$ -switched cells. One ofthe strongly upregulated genes encodes a novel murine CC chemokinewe have named ABCD-1. The ABCD-1 gene has three exons separatedby 1.2- and 2.7-kb introns. It gives rise to a 2.2-kb transcriptcontaining an open reading frame of 276 nucleotides. Two polyadenylationsites are used, giving rise to cDNAs with either 1550 or 1850bp of 3' untranslated regions. The open reading frame encodesa 24 amino acid-long leader peptide and a 68 amino acid-long matureprotein with a predicted molecular mass of 7.8 kD. ABCD-1 mRNAis found in highest quantities in activated splenic B lymphocytesand dendritic cells. Little chemokine mRNA is present in lung,in unstimulated splenic cells, in thymocytes, and in lymph nodecells. No ABCD-1 mRNA is detected in bone marrow, liver, kidney,or brain, in peritoneal exudate cells as well as in the majorityof all unstimulated B lineage cells tested. It is also undetectablein Concanavalin A-activated/IL-2-restimulated splenic T cells,and in bone marrow-derived IL-2-induced natural killer cells andIL-3-activated macrophages. Recombinant ABCD-1 revealed a concentration-dependentand specific migration of activated splenic T lymphoblasts inchemotaxis assays. FACS^® analyses of migrated cells showed no preferential differencein migration of CD4⁺ versus CD8⁺ T cell blasts. Murine as well as human T cells responded to ABCD-1.Freshly isolated cells from bone marrow, thymus, spleen, and lymphnode, IL-2-activated NK cells, and LPS-stimulated splenic cells,all did not show any chemotactic response. Thus, ABCD-1 is thefirst chemokine produced in large amounts by activated B cellsand acting selectively on activated T lymphocytes. Therefore,ABCD-1 is expected to play an important role in the collaborationof dendritic cells and B lymphocytes with T cells in immune responses.

Key words: novel chemokine; activated B cells; dendritic cells; chemotaxis; activated T cells

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