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Blood, 1 October 2008, Vol. 112, No. 7, pp. 2817-2825. Prepublished online as a Blood First Edition Paper on July 31, 2008; DOI 10.1182/blood-2008-05-157396. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-05-157396v1 112/7/2817    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ding, C. Articles by Yan, J. Search for Related Content PubMed PubMed Citation Articles by Ding, C. Articles by Yan, J. Related Collections Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Targeting of antigens to B cells augments antigen-specific T-cell responses and breaks immune tolerance to tumor-associated antigen MUC1 Chuanlin Ding1, Li Wang1,2, Jose Marroquin1, and Jun Yan1,3 1 Tumor Immunobiology Program, James Graham Brown Cancer Center, University of Louisville, KY; 2 Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai, China; and 3 Department of Medicine, University of Louisville, KY B cells are antibody (Ab)–secreting cells as well as potent antigen (Ag)–presenting cells that prime T-cell activation, which evokes great interest in their use for vaccine development. Here, we targeted ovalbumin (OVA) to B cells via CD19 and found that a single low dose of anti–CD19-OVA conjugates, but not isotype mAb-OVA, stimulated augmented CD4 and CD8 T-cell proliferation and expansion. Administration of TLR9 agonist CpG could significantly enhance long-term T-cell survival. Similar results were obtained when the tumor-associated Ag MUC1 was delivered to B cells. MUC1 transgenic (Tg) mice were previously found to lack effective T-cell help and produce low-titer of anti-MUC1 Abs after vaccination. Targeting MUC1 to B cells elicited high titer of anti-MUC1 Abs with different isotypes, predominantly IgG2a and IgG2b, in MUC1 Tg mice. The isotype switching of anti-MUC1 Ab was CD4 dependent. In addition, IFN-–producing CD8 T cells and in vivo cytolytic activity were significantly increased in these mice. The mice also showed significant resistance to MUC1+ lymphoma cell challenge both in the prophylactic and therapeutic settings. We conclude that Ags targeting to B cells stimulate CD4 and CD8 T-cell responses as well as Th-dependent humoral immune responses. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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