PRELYMPHOMATOUS B-CELL HYPERPLASIA IN THE BONE-MARROW OF INTERLEUKIN-7 TRANSGENIC MICE - PRECURSOR B-CELL DYNAMICS, MICROENVIRONMENTAL ORGANIZATION AND OSTEOLYSIS

Transgenic mice carrying mouse interleukin-7 (IL-7) cDNA under the con trol of MHC class II (E alpha) promoter develop B lymphoid tumors. We have analyzed population dynamics of early precursor B cells and elect ron microscopic organization of bone marrow (BM) during the prelymphom atous phase. Immunofluorescence labeling of terminal deoxynucleotidyl transferase (TdT), B220 glycoprotein, and mu heavy chains have been us ed to quantitate three populations of pro-B cells lacking mu chains, c ytoplasmic mu-bearing pre-B cells, and surface mu-bearing B lymphocyte s. Proliferative activity was assayed by metaphase arrest. In BM of IL -7 transgenic mice, the number and proliferative activity of cells in each of the pro-B and pre-B cell populations were markedly increased. B lymphocytes increased to a lesser extent. The BM cavity was consider ably expanded and cortical bone showed focal osteolysis. Immature lymp hoid cells compressed the venous sinusoids and exuded through eroded b one. Apoptotic bodies, macrophages, and plasma cells were unusually pr ominent. B lymphocytes and cells of B precursor phenotype were also mu ch increased in the spleen. These results demonstrate that overexpress ion of IL-7 causes excessive proliferation of a wide range of precurso r B cells in BM. Such prolonged stimulation at early stages of B cell development, prone to genetic errors, may predispose to neoplasia. The bone resorption in these transgenic mice provides a model for bone le sions in BM malignancies.