This award supports a two-year collaborative research project between Max Cooper, M.D., of the University of Alabama at Birmingham and Professor Takeshi Watanabe of Kyushu University. on the analysis of the function of the surface antigen BP-1/6C3 expressed on mouse hematopoietic cells (mostly B-lymphocytes) and analysis of its possible influence on B-lineage differentiation. Cell surface proteins expressed by developing B lymphocyte precursors are involved in regulatory interactions with other cell types in hemopoietic tissues that help orchestrate this entire process. The antigen identified by the BP-1 antibody is a good candidate for this type of function since its expression is restricted to early B-lineage cells, and it may modulate their proliferation. BP-1 is a cell surface metallopeptidase, animopeptidase A (APA). To determine the function of APA in B cell development, two strategies will be followed. First, transgenic mice expressing APA driven by the immunoglobulin heavy chain promoter and enhancer will be constructed. Study of this transgenic mouse model will permit the determination of the effect of prolinged expression of APA beyond the early B cell stage where its expression is normally extinguished. An alternate informative approach will be to disrupt the APA gene by homologous recombination. Since BP-1/APA is expressed in a variety of tissues outside of the homopoietic lineage, these "knockout" mice should also help to define the necessity for and function of this enzyme in other systems. The expertise of the U.S. and Japanese groups is complementary and collaboration has been in progress for several years. Dr. Cooper's group has made appropriate monoclonal antibodies, cloned the corresponding c-DNA, and established its aminopeptidase A activity. Dr. Watanabe's group is well known for their expertise in molecular biology, particularly in the area of B cell gene expression.
