The nonimmunoglobulin portion of lambda5 mediates cell-autonomous pre-B cell receptor signaling.
The pre-B cell receptor (preBCR), composed of mu immunoglobulin (Ig) and surrogate light chains, signals large 'preB-II' cells to proliferate in the apparent absence of ligands or cooperating cells. We deleted the N-terminal, nonimmunoglobulin (nonlg) portion of lambda5, or mutated seven arginine residues in it to serine residues. PreBCRs with such mutant lambda5 proteins showed increased cell surface representation and a diminished rate of aggregation and internalization. Tyrosine phosphorylation of preBCR complexes containing mutant lambda5 proteins was abolished. These results indicate that the nonIg portion of lambda5, and the seven arginine residues in it, are needed for signal transduction, and that signaling could be cell autonomous. We propose two models to explain the apparently constitutive, ligand-independent signal-transducing capacity of the preBCR.
Ohnishi
Kazuo
K
National Institute of Infectious Diseases, Department of Immunology, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan. ohnishik@nih.go.jp
Melchers
Fritz
F
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D004247:DNA / Q000737:chemistry / Q000235:genetics; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000276:immunology; D006801:Humans; D007148:Immunoglobulin mu-Chains / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D054420:Pre-B Cell Receptors; D051381:Rats; D011947:Receptors, Antigen, B-Cell; D016415:Sequence Alignment; D015398:Signal Transduction / Q000276:immunology
D007148:Immunoglobulin mu-Chains; D008562:Membrane Glycoproteins; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell; D004247:DNA