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A critical role of lambda 5 protein in B cell development.

D Kitamura1, A Kudo, S Schaal

  • 1Institute for Genetics, University of Cologne, Germany.

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|May 29, 1992
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Summary

The lambda 5 gene is crucial for B cell development. Its inactivation blocks B cell maturation at the pre-B cell stage, but allows some cells to reach the periphery.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • The lambda 5 gene is homologous to immunoglobulin J lambda-C lambda genes.
  • Lambda 5 protein forms complexes with mu or D mu proteins and Vpre-B protein in immature B cells.

Purpose of the Study:

  • To investigate the role of the lambda 5 gene in B cell development.
  • To determine the consequences of lambda 5 gene inactivation in mice.

Main Methods:

  • Targeted gene disruption of the lambda 5 gene in embryonic stem cells.
  • Generation of genetically modified mice to study B cell development.

Main Results:

  • Inactivation of the lambda 5 gene blocked B cell development at the pre-B cell stage in the bone marrow.
  • A leaky blockade allowed a low rate of B cells to populate the peripheral immune system.
  • These peripheral B cells were allelically excluded and antigen-responsive.

Conclusions:

  • The lambda 5 gene is essential for normal B cell development.
  • Lambda 5 plays a critical role in the pre-B cell stage transition.
  • Despite developmental block, residual B cells exhibit functional characteristics.