ACTIVATION OF B-CELLS AND T-CELLS BY THE CYTOPLASMIC DOMAINS OF THE B-CELL ANTIGEN RECEPTOR PROTEINS IG-ALPHA AND IG-BETA

In addition to membrane immunoglobulin (mIg), the B-cell antigen recep tor contains Ig-alpha/Ig-beta heterodimers that link mIg to intracellu lar signaling molecules. To compare the ability of the cytoplasmic dom ains of Ig-alpha and Ig-beta to transduce signals in B- and T-cells, w e con constructed chimeric genes encoding the extracellular and transm embrane domains of human CD8 alpha and the cytoplasmic domain of murin e Ig-alpha (CD8/Ig-alpha) or Ig-beta (CD8/Ig-beta). In murine B-cell h ybridoma LK 35.2 cells, antibody-mediated cross-linking of mIg, CD8/Ig -alpha, or CD8/Ig-beta induced similar increases in intracellular calc ium levels and protein tyrosine phosphorylation. Substitution of alani ne for the conserved leucine, but not the conserved isoleucine, residu e within the putative activation motif of CD8/Ig-beta destroyed signal ing ability. In murine T-cell hybridoma DO-11.10 cells, cross-linking of the T-cell antigen receptor, CD8/Ig-alpha, or CD8/Ig-beta stimulate d equivalent protein tyrosine phosphorylation and interleukin-2 produc tion. Thus, the cytoplasmic domains of Ig-a! and Ig-p are equally capa ble of initiating early signaling events downstream of B- and T cell a ntigen receptors as well as evoking a complete biological effector res ponse in lymphocytes.