Activation of B- 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 receptor contains Ig-alpha/Ig-beta heterodimers that link mIg to intracellular signaling molecules. To compare the ability of the cytoplasmic domains of Ig-alpha and Ig-beta to transduce signals in B- and T-cells, we constructed chimeric genes encoding the extracellular and transmembrane domains of human CD8 alpha and the cytoplasmic domain of murine Ig-alpha (CD8/Ig-alpha) or Ig-beta (CD8/Ig-beta). In murine B-cell hybridoma LK 35.2 cells, antibody-mediated cross-linking of mIg, CD8/Ig-alpha, or CD8/Ig-beta induced similar increases in intracellular calcium levels and protein tyrosine phosphorylation. Substitution of alanine for the conserved leucine, but not the conserved isoleucine, residue within the putative activation motif of CD8/Ig-beta destroyed signaling 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 stimulated equivalent protein tyrosine phosphorylation and interleukin-2 production. Thus, the cytoplasmic domains of Ig-alpha and Ig-beta are equally capable of initiating early signaling events downstream of B- and T-cell antigen receptors as well as evoking a complete biological effector response in lymphocytes.
Taddie
J A
JA
Molecular Biology and Virology Laboratory, Salk Institute, San Diego, California 92186.
Hurley
T R
TR
Hardwick
B S
BS
Sefton
B M
BM
D000818:Animals; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D051925:CD79 Antigens; D016827:CD8 Antigens / Q000276:immunology; D003432:Cross-Linking Reagents; D017931:DNA Primers; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology; D007930:Leucine / Q000235:genetics; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D014443:Tyrosine / Q000378:metabolism
D015703:Antigens, CD; D051925:CD79 Antigens; C497881:CD79A protein, human; D016827:CD8 Antigens; C497882:Cd79a protein, mouse; D003432:Cross-Linking Reagents; D017931:DNA Primers; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins; D014443:Tyrosine; D007930:Leucine