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Rearrangement of mouse immunoglobulin kappa deleting element recombining sequence promotes immune tolerance and lambda B cell production

Academic Article
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Overview

related to degree

  • Duong, Bao Hoa, Ph.D. in Macromolecular and Cellular Structure and Chemistry, Scripps Research 2003 - 2009
  • Vela, Jose L, Ph.D. in Immunology, Scripps Research 2001 - 2007

authors

  • Vela, Jose L
  • Aft-Azzouzene, D.
  • Duong, Bao Hoa
  • Ota, Takayuki
  • Nemazee, David

publication date

  • February 2008

journal

  • Immunity  Journal

abstract

  • The recombining sequence (RS) of mouse and its human equivalent, the immunoglobulin (Ig) kappa deleting element (IGKDE), are sequences found at the 3' end of the Ig kappa locus (Igk) that rearrange to inactivate Igk in developing B cells. RS recombination correlates with Ig lambda (Iglambda) light (L) chain expression and likely plays a role in receptor editing by eliminating Igk genes encoding autoantibodies. A mouse strain was generated in which the recombination signal of RS was removed, blocking RS-mediated Igk inactivation. In RS mutant mice, receptor editing and self-tolerance were impaired, in some cases leading to autoantibody formation. Surprisingly, mutant mice also made fewer B cells expressing lambda chain, whereas lambda versus kappa isotype exclusion was only modestly affected. These results provide insight into the mechanism of L chain isotype exclusion and indicate that RS has a physiological role in promoting the formation of lambda L chain-expressing B cells.

subject areas

  • Animals
  • Antibodies, Antinuclear
  • B-Lymphocytes
  • Gene Rearrangement, B-Lymphocyte, Light Chain
  • Genes, Immunoglobulin
  • Hybridomas
  • Immune Tolerance
  • Immunoglobulin kappa-Chains
  • Immunoglobulin lambda-Chains
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Recombination, Genetic
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Identity

PubMed Central ID

  • PMC2351955

International Standard Serial Number (ISSN)

  • 1074-7613

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2007.12.011

PubMed ID

  • 18261939
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Additional Document Info

start page

  • 161

end page

  • 170

volume

  • 28

issue

  • 2

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