Tonic BCR signaling represses receptor editing via Raf- and calcium-dependent signaling pathways

Laura B. Ramsey, Amanda L. Vegoe, Andrew T. Miller, Michael P. Cooke, Michael A Farrar

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Light chain receptor editing is an important mechanism that prevents B cell self-reactivity. We have previously shown that tonic signaling through the BCR represses RAG expression at the immature B cell stage, and that initiation of light chain rearrangements occurs in the absence of these tonic signals in an in vitro model of B cell development. To further test our hypothesis we studied the effect of itpkb deficiency (itpkb -/- mice) or Raf hyper-activation (Raf-CAAX transgenic mice), two mutations that enhance BCR signaling, on receptor editing in an in vivo model. This model relies on transferring bone marrow from wild-type or mutant mice into mice expressing an anti-kappa light chain transgene. The anti-kappa transgene induces receptor editing of all kappa light chain expressing B cells, leading to a high frequency of lambda light chain expressing B cells. Anti-κ transgenic recipients of bone marrow from itpkb -/- or Raf-CAAX mice showed lower levels of editing to λ light chain than did non-transgenic control recipients. These results provide evidence in an in vivo model that enhanced BCR signaling at the immature B cell stage of development suppresses light chain receptor editing.

Original languageEnglish (US)
Pages (from-to)74-77
Number of pages4
JournalImmunology Letters
Volume135
Issue number1-2
DOIs
StatePublished - Mar 30 2011

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Keywords

  • Receptor editing
  • Tonic BCR signaling

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