Differential signaling through the Ig-alpha and Ig-beta components of the B cell antigen receptor.
The B cell antigen receptor is a complex containing the antigen-binding immunoglobulin molecules and the Ig-alpha/Ig-beta heterodimer which presumably connects the B cell antigen receptor to intracellular signaling components. To analyze the functional properties of the cytoplasmic parts of the B cell antigen receptor, we used the K46 B lymphoma line (IgG2a, kappa) to express chimeric molecules composed of the extracellular and transmembrane part of the CD8 alpha molecule and the cytoplasmic sequence of either the Ig-alpha (CD8 alpha/Ig-alpha), the Ig-beta (CD8 alpha/Ig-beta) protein or the membrane-bound gamma 2a heavy chain (CD8 alpha/gamma 2a). From these three types of chimeric molecules only (CD8 alpha/Ig-alpha and CD8 alpha/Ig-beta, but not CD8 alpha/gamma 2a, could transduce signals, thus providing the first evidence that the cytoplasmic tail of Ig-alpha and Ig-beta have a signaling capacity. After cross-linking with anti-CD8 alpha antibodies, both molecules induced a similar increase in intracellular free calcium ion and in MAP kinase phosphorylation. Protein tyrosine kinases, however, were strongly activated via the CD8 alpha/Ig-alpha and only marginally via the CD8 alpha/Ig-beta molecule. This suggests that the Ig-alpha and Ig-beta proteins have distinct roles during signal transduction through the B cell antigen receptor.
Kim
K M
KM
Max-Planck Institut für Immunbiologie, Freiburg, FRG.
Alber
G
G
Weiser
P
P
Reth
M
M
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D001483:Base Sequence; D051925:CD79 Antigens; D016827:CD8 Antigens / Q000502:physiology; D002118:Calcium / Q000502:physiology; D003593:Cytoplasm / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D019000:Phosphotyrosine; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction; D014162:Transfection; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D015703:Antigens, CD; D051925:CD79 Antigens; D016827:CD8 Antigens; C497882:Cd79a protein, mouse; C497884:Cd79b protein, mouse; D008562:Membrane Glycoproteins; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D002118:Calcium