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Blood, 1 December 2007, Vol. 110, No. 12, pp. 3815. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal 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 Xu, H. Articles by Ildstad, S. T. Search for Related Content PubMed Articles by Xu, H. Articles by Ildstad, S. T. Related Collections Related Article in Blood Online Social Bookmarking                   What's this? Next Article  IMMUNOBIOLOGY Comment on Li et al, page 3926 Xenotransplantation: a step closer to reality? Hong Xu, Jun Yan, and Suzanne T. Ildstad INSTITUTE FOR CELLULAR THERAPEUTICS; JAMES GRAHAM BROWN CANCER CENTER In this issue of Blood, Li and colleagues describe a critical role for B cells in xenoreactivity and provide evidence for marginal zone B cell–NK cell interactions in the regulation of T-independent xenoantibody production. Solid organ transplantation is the preferred treatment for end-organ failure. Many patients die before a precious organ becomes available due to the donor organ shortage, prompting a strong research focus on xenotransplantation. However, xenotransplantation has remained an elusive goal in solving the organ shortage. Most research to date has focused on preexisting natural antibody and the role of T cells and natural killer (NK) cells in xenoreactivity.1,2 The work of Li and colleagues in this issue of Blood identifies a novel collaboration between marginal zone B (MZB) cells (CD19+CD21highCD23low) and NK cells in the rapid induction of T-cell–independent, non–Gal-xenoantibody production and xenorejection (as shown in the figure). View larger version (154K): [in this window] [in a new window]   The authors have demonstrated a novel interaction between marginal-zone B cells and NK cells in xenotransplantation. They have shown that (A) NK-cell help is required for T-independent xenoantibody production using C57BL/6 nude mice as recipients, and (B) depletion of NK cells abrogates xenoantibody production.   CD154:CD40 is a specific costimulatory pathway in B-cell activation and antibody production in T-cell–dependent allogeneic3 and xenogeneic4 antigens. In their report, Li and colleagues note that the CD154:CD40 pathway seems to be involved in the inducible T-cell–independent xenoantibody response, as it could be partially suppressed by CD154 blockade, providing indirect evidence that this pathway may be involved in the interaction between MZB and NK cells. The interaction between MZB cells and NK cells for xenoantibody production is independent of IFN- production or cytolytic activity by NK cells. These studies suggest that NK cells can regulate MZB-cell function and possibly could be used for cell-based immunotherapy to prevent xenograft rejection. However, caution is needed, given the complexity of non-Gal, T-independent antigens in xenotransplantation. For example, the anti–TNP-Ficoll IgM response is not completely abrogated in MZB-cell–deficient, Pyk-2–deficient mice. Nevertheless, this study provides new insight into the collaborative crosstalk of cell-cell interactions in the regulation of T-independent xenoantibody production. This report also affirms the critical role of B cells not only in allotransplantation,5 but also in xenotransplantation. These findings may provide a mechanistically rational approach for using costimulatory blockade and/or targeting these specific effector cells to promote xenograft acceptance. Perhaps most importantly, Li and colleauges can further test their findings in a normal animal model, which would provide further evidence for their clinical applicability in xenotrans-plantation. Footnotes Conflict-of-interest disclosure: The authors declare no competing financial interests. REFERENCES Bach FH, Robson SC, Winkler H, et al. Barriers to xenotransplantation. Nat Med 1995; 1:869–873.[CrossRef][Medline] [Order article via Infotrieve] Baertschiger RM and Buhler LH. Xenotransplantation literature update September-October 2006. Xenotransplantation 2007; 14:83.[CrossRef][Medline] [Order article via Infotrieve] Bishop GA and Hostager BS. The CD40-CD154 interaction in B cell-T liaisons. Cytokine Growth Factor Rev 2003; 14:297–309.[CrossRef][Medline] [Order article via Infotrieve] Tai H-C, Campanile N, Ezzelarab M, Cooper DKC, Phelps C. Measurement of anti-CD154 monoclonal antibody in primate sera by competitive inhibition ELISA. Xenotransplantation 2006; 13:566–570.[CrossRef][Medline] [Order article via Infotrieve] Xu H, Yan J, Huang H, et al. Co-stimulatory blockade of CD154:CD40 in combination with T-cell lymphodepletion results in prevention of allogeneic sensitization. Blood Prepublished on September 7, 2007, as DOI 10.1182/blood-2006-10-053801.[Abstract/Free Full Text] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Rapidly induced, T-cell–independent xenoantibody production is mediated by marginal zone B cells and requires help from NK cells Shengqiao Li, Yehong Yan, Yuan Lin, Dominique M. Bullens, Omer Rutgeerts, Jozef Goebels, Constant Segers, Louis Boon, Ahmad Kasran, Rita De Vos, Christiane Dewolf-Peeters, Mark Waer, and An D. Billiau Blood 2007 110: 3926-3935. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal 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 Xu, H. Articles by Ildstad, S. T. Search for Related Content PubMed Articles by Xu, H. Articles by Ildstad, S. T. 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