Immunoglobulin receptor signaling depends on the carboxyl terminus but not the heavy-chain class.
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 mu heavy chain was replaced by that of delta, gamma 2b, or alpha heavy chains or that of the I-Ab class II (Ia) alpha 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.
Webb
C F
CF
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.
Nakai
C
C
Tucker
P W
PW
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D003001:Cloning, Molecular; D005455:Fluorescent Antibody Technique; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D007072:Immunoglobulin D / Q000235:genetics / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology*; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000235:genetics / Q000276:immunology; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology; D008223:Lymphoma; D051379:Mice; D008969:Molecular Sequence Data; D010957:Plasmids; D011971:Receptors, Immunologic / Q000276:immunology*; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014162:Transfection; D014407:Tumor Cells, Cultured
D000949:Histocompatibility Antigens Class II; D007072:Immunoglobulin D; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M; D011971:Receptors, Immunologic