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 journalArticlepeer-review

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

Bibliographical note

Funding Information:
We thank J. Bednar, C. Andersen, and R. Agneberg for assistance with animal husbandry, M. Weigert for providing the ακ mice, and B. Schram and T. Behrens for discussion and suggestions. This work was funded by a NIH grant (R01 AR043805) and a Leukemia and Lymphoma Society Scholar award to M.A.F.

Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.

Keywords

  • Receptor editing
  • Tonic BCR signaling

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