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This Article Full Text (PDF) All Versions of this Article: jimmunol.0901175v1 183/11/7140    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Ding, C. Articles by Yan, J. PubMed PubMed Citation Articles by Ding, C. Articles by Yan, J.

Plasmacytoid Dendritic Cells Regulate Autoreactive B Cell Activation via Soluble Factors and in a Cell-to-Cell Contact Manner¹

Chuanlin Ding,^* Yihua Cai,^* Jose Marroquin,^* Suzanne T. Ildstad, and Jun Yan^2*

*Tumor Immunobiology Program, James Graham Brown Cancer Center, Institute for Cellular Therapeutic, Department of Surgery, and Department of Medicine, University of Louisville, Louisville, KY 40202

Plasmacytoid dendritic cells (pDCs) are specialized type I IFN producers, which play an important role in pathogenesis of autoimmune disorders. Dysregulated autoreactive B cell activation is a hallmark in most autoimmune diseases. This study was undertaken to investigate interactions between pDCs and autoreactive B cells. After coculture of autoreactive B cells that recognize self-Ag small nuclear ribonucleoprotein particles with activated pDCs, we found that pDCs significantly enhance autoreactive B cell proliferation, autoantibody production, and survival in response to TLR and BCR stimulation. Neutralization of IFN-/β and IL-6 abrogated partially pDC-mediated enhancement of autoreactive B cell activation. Transwell studies demonstrated that pDCs could provide activation signals to autoreactive B cells via a cell-to-cell contact manner. The involvement of the ICAM-1-LFA-1 pathway was revealed as contributing to this effect. This in vitro enhancement effect was further demonstrated by an in vivo B cell adoptive transfer experiment, which showed that autoreactive B cell proliferation and activation were significantly decreased in MyD88-deficient mice compared with wild-type mice. These data suggest the dynamic interplay between pDCs and B cells is required for full activation of autoreactive B cells upon TLR or BCR stimulation.

Correspondence: ² Address correspondence and reprint requests to Dr. Jun Yan, Tumor Immunobiology Program, James Graham Brown Cancer Center, Delia D. Baxter Research Building, Room 119A, University of Louisville, 580 South Preston Street, Louisville, KY 40202. E-mail address: jun.yan{at}louisville.edu

¹ This study was supported by research funding from American College of Rheumatology and Arthritis Foundation. J.Y. is a recipient of American College of Rheumatology and Arthritis Foundation Investigator Award. This research was supported in part by National Institutes of Health Grants R01 DK52294 and HL63442 and by the University of Louisville Hospital to S.T.I. C.D. is a recipient of Arthritis Foundation Postdoctoral Fellowship Award.