Submitted January 4, 2007
Accepted July 4, 2007
Rapidly induced, T-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
Laboratory of Experimental Transplantation, University of Leuven, Leuven, Belgium
Laboratory of Experimental Immunology, University of Leuven, Leuven, Belgium
Bioceros BV, Utrecht, Netherlands
Morphology and Molecular Pathology, University of Leuven, Leuven, Belgium
* Corresponding author; email: mark.waer{at}gbiomed.kuleuven.be.
Xenoantibody production directed at a wide variety of T lymphocyte-dependent and T lymphocyte-independent xenoantigens remains the major immunological obstacle for successful xenotransplantation. The B lymphocyte subpopulations and their helper factors, involved in T-independent xenoantibody production are only partially understood and their identification will contribute to the clinical applicability of xenotransplantation. Here we show, using models involving T cell-deficient athymic recipient mice, that rapidly induced, T cell-independent xenoantibody production is mediated by Marginal Zone B lymphocytes and required help from Natural Killer cells. This collaboration neither required Natural Killer cell-mediated IFN-
production, nor Natural Killer cell-mediated cytolytic killing of xenogeneic target cells. The T-independent IgM xenoantibody response could be partially suppressed by CD40L-blockade.
