Correction of the TNF-LTα-Deficient Phenotype by Bone Marrow Transplantation

Mice with inactivated TNF-LTα genes have profound abnormalities of the immune system with hypoimmunoglobulinaemia, lack of lymph nodes, undifferentiated spleen, and defective Ig class switch. Transplantation of bone marrow cells from wild-type mice restored the synthesis of TNF, corrected the splenic microarchitecture, repopulated the lamina propria with IgA-producing plasma cells, and normalized the serum immunoglobulin levels of TNF-LTα deficient mice. Furthermore, the formation of germinal centers in the spleen and the defective Ig class switch in response to a T-cell-dependent antigen is corrected. These data demonstrate that most TNFproducing cells are bone-marrow-derived, and that the immunodeficiency due to TNF-LTα deletion can be corrected to a large extent by normal bone marrow, cell transplantation.