Rapidly induced, T-cell–independent xenoantibody production is mediated by marginal zone B cells and requires help from NK cells

• Published in: Blood 2007-12, Vol.110 (12), p.3926-3935
• Main Authors: Li, Shengqiao, Yan, Yehong, Lin, Yuan, Bullens, Dominique M., Rutgeerts, Omer, Goebels, Jozef, Segers, Constant, Boon, Louis, Kasran, Ahmad, De Vos, Rita, Dewolf-Peeters, Christiane, Waer, Mark, Billiau, An D.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Heterophile - immunology; Antibody Formation - genetics; B-Lymphocytes - cytology; B-Lymphocytes - immunology; CD40 Ligand - antagonists & inhibitors; CD40 Ligand - immunology; Cell Communication - immunology; Immunoglobulin M - immunology; Killer Cells, Natural - cytology; Killer Cells, Natural - immunology; Mice; Mice, Knockout; Mice, Nude; Models, Immunological; T-Lymphocytes - immunology; Transplantation, Heterologous - immunology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2007-01-065482

Xenoantibody production directed at a wide variety of T lymphocyte–dependent and T lymphocyte–independent xenoantigens remains the major immunologic obstacle for successful xenotransplantation. The B lymphocyte subpopulations and their helper factors, involved in T-cell–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 requires help from natural killer (NK) cells. This collaboration neither required NK-cell–mediated IFN-γ production, nor NK-cell–mediated cytolytic killing of xenogeneic target cells. The T-cell–independent IgM xenoantibody response could be partially suppressed by CD40L blockade.