AND B-CELL DEVELOPMENT IN BP-1 6C3/AMINOPEPTIDASE A-DEFICIENT MICE/

Stage-restricted expression of cell surface molecules serves to deline ate B lineage cells during their progressive differentiation within th e bone marrow, The BP-1/6C3 Ag, aminopeptidase A (APA), is selectively expressed by the pre-B and immature B cells. This ectoenzyme, which i s also present on bone marrow-derived stromal cells, thymic cortical e pithelial cells,renal proximal tubular cells, intestinal enterocytes, and endothelial cells, cleaves acidic glutamyl and aspartyl residues f rom the N-terminus of angiotensin and other biologically active peptid es to quench their functional activity, BP-1/6C3/APA expression by ear ly B lineage cells is up-regulated by IL-7, an important growth factor for pre-B cells and T cells. To explore the physiologic role of this peptidase, we generated a mouse model of BP-1 deficiency by gene targe ting in embryonal stem cells. While mice homozygous for the BP-1 mutat ion did not express detectable BP-I protein or enzyme activity, they d eveloped normally, generated normal numbers of T and B cells, exhibite d integrity of Ab responses to both thymus-dependent and -independent Ags; and produced normal serum Ig levels. Phenotypic analysis of bone marrow and thymic lymphocytes indicated a normal pattern of B and T li neage differentiation. B lymphopoiesis in fetal liver cultures and the proliferative responses of bone marrow cells to IL-7 and LPS were als o unimpaired, These findings indicate that BP-1 ectoenzyme activity is not essential for normal B and T cell development.