Immunoglobulin Receptor Signaling Depends on the Carboxyl Terminus but not the Heavy-Chain Class

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 86; no. 6; pp. 1977 - 1981
• Main Authors: Webb, Carol F., Nakai, Chieko, Tucker, Philip W.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01-03-1989; National Acad Sciences
• Subjects: Amino Acid Sequence; Amino acids; Animals; Antibodies; B lymphocytes; B-Lymphocytes - immunology; Biological and medical sciences; Cell Division; Cell lines; Cell receptors; Cell structures and functions; Cellular immunity; Cloning, Molecular; Fc receptors; Fluorescent Antibody Technique; Fluorescent antibody techniques; Fundamental and applied biological sciences. Psychology; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - immunology; Immunoglobulin D - genetics; Immunoglobulin D - immunology; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Heavy Chains - immunology; Immunoglobulin Idiotypes - immunology; Immunoglobulin Isotypes - genetics; Immunoglobulin Isotypes - immunology; Immunoglobulin M - genetics; Immunoglobulin M - immunology; Isotypes; lymphocytes B; Lymphoma; Mice; Molecular and cellular biology; Molecular Sequence Data; Molecules; Plasmids; Receptors; Receptors, Immunologic - immunology; Signal Transduction; Signals; Structure-Activity Relationship; Transfection; Tumor Cells, Cultured; C terminal-Sequence; Vertebrata; Mammalia; Transfection; Mouse; Antibody; Rodentia; Gene organization; Idiotypy; Immunofluorescence; Biological receptor
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.86.6.1977

To examine the isotypic and structural requirements involved in signaling through the immunoglobulin (Ig) receptor on B lymphocytes, we established a panel of T15 idiotype-positive transfectants that expressed wild-type IgM, wild-type IgD, or hybrid IgM molecules. Growth inhibition of the transfected lymphoma cells in response to anti-idiotype antibodies was used to measure signaling. Hybrid IgM molecules were constructed so that the membrane-spanning region of the μ heavy chain was replaced by that of δ , γ 2b, or α heavy chains or that of the I-Ab class II (Ia) α chain. All transfectants that expressed IgM or hybrid IgM molecules with membrane-spanning regions from another Ig isotype underwent signaling in response to anti-idiotype antibodies, whereas the IgM-Ia hybrid transfectants did not. Transfectants that expressed wild-type IgD molecules also underwent signaling, although this response was particularly sensitive to serum concentrations. These results imply that signaling occurs in a similar manner through heavy-chain receptors of any isotype and suggest that conserved amino acid sequences in the transmembrane regions are important in this process.