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The nonimmunoglobulin portion of λ5 mediates cell-autonomous pre-B cell receptor signaling

Nature Immunology volume 4, pages 849–856 (2003)Cite this article

Abstract

The pre-B cell receptor (preBCR), composed of μ 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 λ5, or mutated seven arginine residues in it to serine residues. PreBCRs with such mutant λ5 proteins showed increased cell surface representation and a diminished rate of aggregation and internalization. Tyrosine phosphorylation of preBCR complexes containing mutant λ5 proteins was abolished. These results indicate that the nonIg portion of λ5, 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.

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Figure 1: Structures of wild-type and mutant forms of λ5.
Figure 2: Surface expression of preBCR in Abelson virus–transformed λ5−/− pre-B cells.
Figure 3: Confocal fluorescence microscopy of preBCR deposition on the surface of preB cells.
Figure 4: Comparison of Endo H sensitivity, receptor internalization rate and tyrosine phosphorylation of wild-type and mutant preBCRs.
Figure 5: Wild-type preBCR forms large aggregates.
Figure 6: Hypothetical models for preB cell autonomous cross-linking of preBCR by electrostatic interaction of nonlg domains of λ5.

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Acknowledgements

We thank H. Karasuyama for the SL156 and LM34 antibodies; and T. Takemori and K. Karjalainen for advice and discussions. This work was supported in part by grants to F.M. from the Swiss National Funds (No-3100-066682.01/1) and to K.O. from the Japan Society for the Promotion of Science (KAKENHI 14570290).

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  1. Department of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo, 162-8640, Japan

    Kazuo Ohnishi

  2. Department of Cell Biology, Biozentrum, University of Basel, Klingelbergstrasse 50/70, Basel, CH-4056, Switzerland

    Fritz Melchers

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Correspondence to Kazuo Ohnishi.

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Ohnishi, K., Melchers, F. The nonimmunoglobulin portion of λ5 mediates cell-autonomous pre-B cell receptor signaling. Nat Immunol 4, 849–856 (2003). https://doi.org/10.1038/ni959

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