NZB mice exhibit a primary T cell defect in fetal thymic organ culture.

Document Type


Publication Date



Bone-Marrow-Cells, Cell-Differentiation, Histocompatibility-Testing, Leukopoiesis, Lymphopenia, Mice, Mice-Inbred-BALB-C, Mice-Inbred-C57BL, Mice-Inbred-NZB, Organ-Culture, Stem-Cells, SUPPORT-U-S-GOVT-P-H-S, T-Lymphocytes, Thymus-Gland

JAX Source

J Immunol 2000 Feb; 164(3):1569-75.




Defects in T cell development have been suggested to be a factor in the development of systemic autoimmunity in NZB mice. However, the suggestion of a primary T cell defect has often been by extrapolation, and few direct observations of T cell precursors in NZB mice have been performed. Moreover, the capacity of NZB bone marrow T cell precursors to colonize the thymus and the ability of the NZB thymic microenvironment to support T lymphopoiesis have not been analyzed. To address this important issue, we employed the fetal thymic organ culture system to examine NZB T cell development. Our data demonstrated that NZB bone marrow cells were less efficient at colonizing fetal thymic lobes than those of control BALB/c or C57BL/6 mice. In addition, NZB bone marrow cells did not differentiate into mature T cells as efficiently as bone marrow cells from BALB/c or C57BL/6 mice. Further analysis revealed that this defect resulted from an intrinsic deficiency in the NZB Lin-Sca-1+c-kit+ bone marrow stem cell pool to differentiate into T cells in fetal thymic organ culture. Taken together, the data document heretofore unappreciated deficiencies in T cell development that may contribute to the development of the autoimmune phenotype in NZB mice.

Please contact the Joan Staats Library for information regarding this document.