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Essential roles of the κ light chain intronic enhancer and 3′ enhancer in κ rearrangement and demethylation

Nature Immunology volume 3, pages 463468 (2002) | Download Citation

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Abstract

The κ intronic (MiEκ) and 3′ (3′Eκ) enhancers are both quantitatively important to, but not essential for, immunoglobulin κ rearrangement. To determine the functional redundancy between these two enhancers, B cells derived from mutant embryonic stem cells—in which both MiEκ and 3′Eκ were deleted on both κ alleles—were analyzed for κ rearrangement. Our findings indicate that these double-mutant B cells have essentially no κ rearrangement but do rearrange and express λ. Therefore, these two κ enhancers share essential roles in activating VκJκ rearrangement. Our findings also indicate that the two κ enhancers play overlapping and distinct roles in the demethylation of κ in B cells.

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Acknowledgements

We thank M. Schlissel for 3′Eκ−/− mice and members of Alt laboratory for critical reading of this manuscript. Supported by NIH grant AI44838 (to Y. X.).

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Affiliations

  1. Section of Molecular Biology, Division of Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0322, USA.

    • Matthew Inlay
    •  & Yang Xu
  2. The Center for Blood Research, The Children's Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.

    • Frederick W. Alt
  3. Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.

    • David Baltimore

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The authors declare no competing financial interests.

Corresponding author

Correspondence to Yang Xu.

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DOI

https://doi.org/10.1038/ni790