The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/8/451/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 3, August 3, 1998 451-463

Articles

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

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

From the * Basel Institute for Immunology, CH-4005, Basel, Switzerland; and the {ddagger} 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-CD40 and interleukin (IL)-4 to mature Sµ-S{varepsilon}–switched cells. One of the strongly upregulated genes encodes a novel murine CC chemokine we have named ABCD-1. The ABCD-1 gene has three exons separated by 1.2- and 2.7-kb introns. It gives rise to a 2.2-kb transcript containing an open reading frame of 276 nucleotides. Two polyadenylation sites are used, giving rise to cDNAs with either 1550 or 1850 bp of 3' untranslated regions. The open reading frame encodes a 24 amino acid–long leader peptide and a 68 amino acid–long mature protein with a predicted molecular mass of 7.8 kD. ABCD-1 mRNA is found in highest quantities in activated splenic B lymphocytes and dendritic cells. Little chemokine mRNA is present in lung, in unstimulated splenic cells, in thymocytes, and in lymph node cells. No ABCD-1 mRNA is detected in bone marrow, liver, kidney, or brain, in peritoneal exudate cells as well as in the majority of all unstimulated B lineage cells tested. It is also undetectable in Concanavalin A–activated/IL-2–restimulated splenic T cells, and in bone marrow–derived IL-2–induced natural killer cells and IL-3–activated macrophages. Recombinant ABCD-1 revealed a concentration-dependent and specific migration of activated splenic T lymphoblasts in chemotaxis assays. FACS® analyses of migrated cells showed no preferential difference in 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 lymph node, IL-2–activated NK cells, and LPS-stimulated splenic cells, all did not show any chemotactic response. Thus, ABCD-1 is the first chemokine produced in large amounts by activated B cells and acting selectively on activated T lymphocytes. Therefore, ABCD-1 is expected to play an important role in the collaboration of dendritic cells and B lymphocytes with T cells in immune responses.

Key Words: novel chemokine • activated B cells • dendritic cells • chemotaxis • activated T cells

Address correspondence to Christoph Schaniel, Basel Institute for Immunology, Grenzacherstrasse 487, Basel, CH-4005, Switzerland. Phone: 41-61-605-1265; Fax: 41-61-605-1364; E-mail: schaniel{at}bii.ch; or Paschalis Sideras, Department of Applied Cell and Molecular Biology, Division of Tumour Biology, Umeå University, 901 87 Umeå, Sweden. Phone: 46-90-10-2524; Fax: 46-90-77-1420; E-mail: paschalis.sideras{at}cmb.umu.se

The Basel Institute for Immunology was founded and is supported by F. Hoffmann-La Roche Ltd., Basel, Switzerland. P. Sideras, E. Pardali, and M. Speletas were supported by the Swedish Medical Research Council (MFR), the Swedish Cancer Foundation "Cancerfonden," and the "Petrus and Augusta Hedlund"-Stiftelsen.

C. Schaniel and E. Pardali contributed equally to this work.

Abbreviations used: BCA-1, B cell–attracting chemokine 1; BLC, B lymphocyte chemoattractant; BLR, Burkitt's lymphoma receptor; DC, dendritic cell(s); FDC, follicular dendritic cell(s); FPLC, fast-performance liquid chromatography; MCP, monocyte chemotactic protein; MDC, macrophage-derived chemokine; MIP, macrophage-inflammatory protein; RAG, recombination activating gene; RANTES, regulated upon activation, normal T cell expressed and secreted; RT, reverse transcription; STCP-1, stimulated T cell chemotactic protein 1; TARC, thymus and activation–regulated chemokine.


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