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Early B cell development requires mu signaling

A Iglesias1, A Nichogiannopoulou, G S Williams

  • 1Max Planck-Institut für Immunobiologie, Freiburg, FRG.

European Journal of Immunology
|October 1, 1993
PubMed
Summary
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Wild-type mu chains, but not mutant mu delta 1, induce immunoglobulin light chain gene rearrangement by associating with the Ig alpha/Ig beta co-receptor. This association is crucial for normal B cell development and differentiation.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • B cell development requires immunoglobulin (Ig) light (L) chain gene rearrangement.
  • The pre-B cell receptor (pre-BCR) plays a critical role in signaling for B cell maturation.
  • The composition and function of the pre-BCR, particularly the interaction of mu heavy chains with the Ig alpha/Ig beta co-receptors, are key areas of investigation.

Purpose of the Study:

  • To investigate the role of wild-type mu and mutant mu delta 1 heavy chains in immunoglobulin light chain gene rearrangement and B cell development.
  • To determine the association of mu and mu delta 1 chains with the Ig alpha/Ig beta co-receptor complex.
  • To elucidate the signaling requirements for pre-B cell differentiation.

Main Methods:

  • In vitro studies using Abelson murine leukemia virus (AMuLV)-transformed murine pre-B cell lines.

Related Experiment Videos

  • Co-precipitation assays to detect protein-protein interactions between mu chains and Ig beta.
  • Analysis of B cell development in transgenic mice expressing wild-type mu or mu delta 1 transgenes.
  • Flow cytometry to assess cell surface marker expression and developmental stages.

    • Main Results:

    • Wild-type mu chains, but not mu delta 1 chains, efficiently induced Ig light chain gene rearrangement in pre-B cell lines.
    • Only wild-type mu chains associated with the Ig alpha/Ig beta co-receptor complex on the surface of pre-B cells.
    • Mutant mu delta 1 chains were expressed on the cell surface via a glycophospholipid anchor.
    • Transgenic mice expressing mu delta 1 showed a block in B cell differentiation at the pre-B to immature B cell transition stage.
    • The mu delta 1 block occurred at the developmental stage critical for light chain gene rearrangement.

    Conclusions:

    • Association of wild-type mu heavy chains with the Ig alpha/Ig beta co-receptor is essential for initiating immunoglobulin light chain gene rearrangement.
    • Signals mediated by the mu/Ig alpha/Ig beta complex are critical for the differentiation of pre-B lymphocytes.
    • The glycophospholipid-anchored mu delta 1 chains are functionally deficient in mediating pre-BCR signaling required for normal B cell maturation.