CD19 is a B-cell-specific member of the immunoglobulin superfamily expressed from early pre-B-cell development until plasma cell differentiation. In vitro studies demonstrate that the CD19 signal transduction molecule can serve as a costimulatory molecule for activation through other B-lymphocyte cell surface molecules. However, much remains to be known regarding how CD19 functions in vivo and whether CD19 has different roles at particular stages of B-cell differentiation. Therefore, transgenic mice overexpressing the human CD19 (hCD19) gene were generated to determine whether this transgene would be expressed in a B-lineage-specific fashion and to dissect the in vivo role of CD19 in B-cell development and activation. Expression of the human transgene product was specifically restricted to all B-lineage cells and appeared early in development as occurs with hCD19. In addition, expression of hCD19 severely impaired the development of immature B cells in the bone marrow, with dramatically fewer B cells found in the spleen, peripheral circulation, and peritoneal cavity. CD19 (48,50), and the cytoplasmic domain of CD19 contains kinase insert regions that when phosphorylated mediate the binding and activation of phosphatidylinositol 3-kinase (47). Thus, although the precise in vivo function of CD19 has not been definitively elucidated, these studies support the hypothesis that the CD19 complex can serve an accessory role in conjunction with surface Ig to enhance antigen-driven B-cell activation (6).Although CD19 is one of the first lineage-specific surface molecules expressed during early pre-B-cell development, little is known about the functional importance of this molecule during early B-cell differentiation or the role of CD19 in vivo. However, the expression of cloned genes in transgenic mice can provide a direct readout of biological consequences of receptor function rather than the effects evoked following cross-linking of a receptor with MAb as has primarily been the approach for examining CD19 function. Further, the mouse model allows an analysis of the complex signaling pathways that occur during early B-cell hematopoiesis for which satisfactory tissue culture models do not exist. Therefore, the human CD19 (hCD19) gene was microinjected into mouse 3884 on April 4, 2019 by guest