Losing your nerves? Maybe it's the antibodies

Nat Rev Immunol. 2009 Jun;9(6):449-56. doi: 10.1038/nri2529.


We propose that the normal immunocompetent B cell repertoire is replete with B cells making antibodies that recognize brain antigens. Although B cells that are reactive with self antigen are normally silenced during B cell maturation, the blood-brain barrier (BBB) prevents many brain antigens from participating in this process. This enables the generation of a B cell repertoire that is sufficiently diverse to cope with numerous environmental challenges. It requires, however, that the integrity of the BBBs is uninterrupted throughout life to protect the brain from antibodies that crossreact with microorganisms and brain antigens. Under conditions of BBB compromise, and during fetal development, we think that these antibodies can alter brain function in otherwise healthy individuals.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoantibodies / immunology*
  • Autoantigens / immunology*
  • B-Lymphocytes / immunology*
  • Blood-Brain Barrier / immunology*
  • Brain / immunology
  • Brain / physiology*
  • Humans
  • Receptors, N-Methyl-D-Aspartate / immunology
  • Receptors, N-Methyl-D-Aspartate / metabolism


  • Autoantibodies
  • Autoantigens
  • Receptors, N-Methyl-D-Aspartate