T and B cell development in BP-1/6C3/aminopeptidase A-deficient mice.
Stage-restricted expression of cell surface molecules serves to delineate B lineage cells during their progressive differentiation within the bone marrow. The BP-1/6C3 Ag, aminopeptidase A (APA), is selectively expressed by the pre-B and immature B cells. This ectoenzyme, which is also present on bone marrow-derived stromal cells, thymic cortical epithelial cells, renal proximal tubular cells, intestinal enterocytes, and endothelial cells, cleaves acidic glutamyl and aspartyl residues from the N-terminus of angiotensin and other biologically active peptides to quench their functional activity. BP-1/6C3/APA expression by early 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 targeting in embryonal stem cells. While mice homozygous for the BP-1 mutation did not express detectable BP-1 protein or enzyme activity, they developed normally, generated normal numbers of T and B cells, exhibited 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 lineage differentiation. B lymphopoiesis in fetal liver cultures and the proliferative responses of bone marrow cells to IL-7 and LPS were also unimpaired. These findings indicate that BP-1 ectoenzyme activity is not essential for normal B and T cell development.
Lin
Q
Q
Department of Medicine, University of Alabama at Birmingham, 35294-3300, USA.
Taniuchi
I
I
Kitamura
D
D
Wang
J
J
Kearney
J F
JF
Watanabe
T
T
Cooper
M D
MD
D000626:Aminopeptidases / Q000172:deficiency / Q000502:physiology*; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D004268:DNA-Binding Proteins; D043384:Glutamyl Aminopeptidase; D006410:Hematopoiesis; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D013601:T-Lymphocytes / Q000502:physiology*
D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D000626:Aminopeptidases; C513548:Enpep protein, mouse; D043384:Glutamyl Aminopeptidase