REGULATION OF B-LYMPHOCYTE DEVELOPMENT AND ACTIVATION BY THE CD19 CD21/CD81/LEU-13 COMPLEX REQUIRES THE CYTOPLASMIC DOMAIN OF CD19/

B lymphocyte development and function are regulated in part by II-re C D19 cell surface receptor complex, which is composed of at least four proteins; CD19, CD21 (CR2, complement receptor 2), CD81, and Leu 13. B ecause this complex has eight membrane-spanning domains and six cytopl asmic regions, determining the molecular basis for its function and si gnal transduction activities has Plot been straightforward. In this st udy, the contribution of the CD19 cytoplasmic domain to the in vivo fu nction of the CD19/CD21/CD81/Leu 13 complex was assessed by generating CD19-deficient mice that expressed a transgene that encoded only the extracellular and transmembrane domains of CD19. Mice expressing this transgene were similar, if not identical, to CD19-deficient mice with abnormal B cell development, a lack of B-1 cells, increased surface Ig M levels on B cells, modest mitogen responses, minimal serum Ig levels , and low humoral immune responses, The results of this study indicate that specific signals generated through the cytoplasmic domain of CD1 9 are essential for B lymphocyte development and function, and that CD 19 is the dominant signaling component of the CD19 complex, Moreover, expression of the CD19 cytoplasmic domain is required for optimal sign aling through the B cell Ag receptor complex.