ABNORMAL-DEVELOPMENT AND DIFFERENTIATION OF MACROPHAGES AND DENDRITICCELLS IN VIABLE MOTH-EATEN MUTANT MICE DEFICIENT IN HEMATOPOIETIC-CELL PHOSPHATASE

In mice homozygous for the 'viable motheaten' (me(v)) mutation, number s of macrophage progenitor cells, particularly monocytes, were markedl y increased in the bone marrow and spleen. Increased mobilization of t hese precursor cells to peripheral tissues and their differentiation t o macrophages were evidenced by striking increases in macrophage numbe rs. Immunohistochemical double staining of tissue sections and flow cy tometry analyses of single cell suspensions from these mice demonstrat ed CD5(Ly-1)-positive macrophages in the peritoneal cavity, spleen and other tissues. Ly-1-positive macrophage precursor cells were demonstr ated in the peritoneal cavity of the me(v) mice and developed in the o mental milky spots. The development of marginal metallophilic and marg inal zone macrophages was poor in the splenic white pulp and related m acrophage populations were absent in the other lymphoid tissues. The n umbers of epidermal Langerhans cells in the skin and T cell-associated dendritic cells in the thymic medulla, lymph nodes, and the other per ipheral lymphoid tissues were decreased. However, increased numbers of dendritic cells accumulated in the lungs, liver, and kidneys. These a bnormalities in development and differentiation of macrophages and den dritic cells may be ascribed to the deficiency in haematopoietic cell SHP-1 tyrosine phosphatase or may be a secondary consequence of abnorm al microenvironments, (either constitutive or in response to inflammat ory stimuli) in the haematopoietic and lymphopoietic organs and tissue s of these mice.