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The Ig alpha/Igbeta heterodimer on mu-negative proB cells is competent for transducing signals to induce early B cell

K Nagata1, T Nakamura, F Kitamura

  • 1Department of Immunology, The Tokyo Metropolitan Institute of Medical Science, Japan.

Immunity
|November 14, 1997
PubMed

Insights

Cross-linking immunoglobulin beta (Ig beta) on proB cells triggers signaling pathways, promoting differentiation. This suggests Ig beta plays a key role in B cell development, similar to the preB cell receptor.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • The immunoglobulin alpha (Ig alpha)/Ig beta heterodimer is present on mu-negative proB cell lines.
  • Calnexin is associated with the Ig alpha/Ig beta heterodimer on these cells.

Purpose of the Study:

  • To investigate the signaling pathways activated by Ig beta cross-linking on proB cells.
  • To determine the role of Ig beta in B cell development, particularly in recombination activating gene (RAG)-2-deficient mice.

Main Methods:

  • Detection of Ig alpha/Ig beta heterodimer on proB cell lines.
  • Cross-linking of Ig beta on proB cells from RAG-2-deficient mice.
  • Analysis of protein tyrosine phosphorylation (Syk, PI3-kinase, Vav, SLP-76) and MAP kinase activation (ERK, JNK/SAPK, p38).
  • Treatment of RAG-2-deficient mice with anti-Ig beta monoclonal antibody to assess B cell differentiation.

Main Results:

  • Ig beta cross-linking induced rapid tyrosine phosphorylation of Ig alpha and intracellular proteins (Syk, PI3-kinase, Vav, SLP-76).
  • Phosphorylation and activation of MAP kinase ERK, but not JNK/SAPK or p38, were observed.
  • Treatment with anti-Ig beta antibody induced differentiation of arrested proB cells to the preB cell stage in RAG-2-deficient mice.

Conclusions:

  • Ig beta cross-linking on proB cells initiates signaling cascades involving tyrosine kinases and MAP kinases.
  • These signals promote differentiation of proB cells to the preB cell stage.
  • The function of Ig beta in proB cells mimics that of the preB cell receptor in normal B cell development.

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