Endogenous antibodies promote rapid myelin clearance and effective axon regeneration after nerve injury

Proc Natl Acad Sci U S A. 2010 Jun 29;107(26):11993-8. doi: 10.1073/pnas.1001948107. Epub 2010 Jun 14.


Degenerating myelin inhibits axon regeneration and is rapidly cleared after peripheral (PNS) but not central nervous system (CNS) injury. To better understand mechanisms underlying rapid PNS myelin clearance, we tested the potential role of the humoral immune system. Here, we show that endogenous antibodies are required for rapid and robust PNS myelin clearance and axon regeneration. B-cell knockout JHD mice display a significant delay in macrophage influx, myelin clearance, and axon regeneration. Rapid clearance of myelin debris is restored in mutant JHD mice by passive transfer of antibodies from naïve WT mice or by an anti-PNS myelin antibody, but not by delivery of nonneural antibodies. We demonstrate that degenerating nerve tissue is targeted by preexisting endogenous antibodies that control myelin clearance by promoting macrophage entrance and phagocytic activity. These results demonstrate a role for immunoglobulin (Ig) in clearing damaged self during healing and suggest that the immune-privileged status of the CNS may contribute to failure of CNS myelin clearance and axon regeneration after injury.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autoantibodies / metabolism*
  • Axons / immunology*
  • Axons / physiology*
  • B-Lymphocytes / immunology
  • Bone Marrow Transplantation
  • Immunity, Humoral
  • Immunization, Passive
  • Macrophages / immunology
  • Macrophages / physiology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Myelin Proteins / immunology*
  • Myelin Proteins / metabolism*
  • Nerve Regeneration / immunology*
  • Nerve Regeneration / physiology*
  • Sciatic Nerve / immunology
  • Sciatic Nerve / injuries
  • Sciatic Nerve / physiopathology


  • Autoantibodies
  • Myelin Proteins