Autoreactive B cell receptors mimic autonomous pre-B cell receptor signaling and induce proliferation of early B cells

Immunity. 2008 Dec 19;29(6):912-21. doi: 10.1016/j.immuni.2008.10.013. Epub 2008 Dec 11.


The majority of early immature B cells express autoreactive B cell receptors (BCRs) that are, according to the current view, negatively selected to avoid the production of self-reactive antibodies. Here, we show that polyreactive BCRs, which recognize multiple self-antigens, induced autonomous signaling and selective expansion of B cell precursors in a manner comparable to the pre-BCR. We found that the pre-BCR was capable of recognizing multiple self-antigens and that a signaling-deficient pre-BCR lacking the non-Ig region of the surrogate-light-chain component lambda5 was rescued by the complementarity-determining region 3 derived from heavy chains of polyreactive receptors. Importantly, bone marrow B cells from mice carrying Ig transgenes for an autoreactive BCR showed increased cell-cycle activity, which could not be detected in cells lacking the transgenic BCR. Together, the pre-BCR has evolved to ensure self-recognition because autoreactivity is required for positive selection of B cell precursors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / immunology
  • Animals
  • Autoantigens / immunology*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Cell Line
  • DNA-Binding Proteins / genetics
  • Mice
  • Mice, Transgenic
  • Molecular Mimicry* / genetics
  • Pre-B Cell Receptors / genetics
  • Pre-B Cell Receptors / immunology*
  • Receptors, Antigen, B-Cell / genetics
  • Receptors, Antigen, B-Cell / immunology*
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction


  • Adaptor Proteins, Signal Transducing
  • Autoantigens
  • B cell linker protein
  • DNA-Binding Proteins
  • Pre-B Cell Receptors
  • Rag2 protein, mouse
  • Receptors, Antigen, B-Cell
  • Recombinant Fusion Proteins