Analysis of NZB hyperdiploid spleen cells

In order to study the cell types involved in the hyper-diploidy characteristic of NZB mice, flow cytometric techniques, which measure the DNA content of individual cells, have been used together with standard cytogenetic analysis. The aneuploid cells present in NZB mice were found to be clonally derived. These cells were of large size relative to nonaneuploid cells. They could not be removed by lysis with anti-Thy 1 plus complement nor were they present in the nylon-wool column nonadherent fraction, both of which are characteristic of T cells. By further cytotoxic analysis, the aneuploid cells were found not to express Ly-5 nor NK surface antigens, found on natural killer cells. The aneuploid cells had increased quantities of cell surface H-2 antigen. This marked susceptibility to lysis with anti-H-2 serum was associated with one or more extra copies of chromosome 17, which carries the H-2 complex. A large proportion of these cells also expressed surface Ia and Ig. The aneuploid cells found in the spleens of older NZB mice derive from bone marrow stem cells. Neonatally thymectomized and lethally irradiated NZB X DBA/2 recipients of anti-Thy-1 treated young NZB bone marow cells ultimately developed aneuploid spleen cells. Such cells are not found in intact or thymectomized NZB x DBA/2 mice nor in recipients of DBA/2 marrow. Finally, congenic NZB mice carrying the CBA/N xid failed to develop aneuploidy. Taken together, these studies suggest that the aneuploid cell is a bone marrow-derived stem cell destined to differentiate into the B cell subset lacking in CBA/N mice.