Endogenous antibodies promote rapid myelin clearance and effective axon regeneration after nerve injury
- 14 June 2010
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 107 (26), 11993-11998
- https://doi.org/10.1073/pnas.1001948107
Abstract
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.Keywords
This publication has 29 references indexed in Scilit:
- B cells produce pathogenic antibodies and impair recovery after spinal cord injury in miceJCI Insight, 2009
- Spinal cord injury triggers systemic autoimmunity: evidence for chronic B lymphocyte activation and lupus‐like autoantibody synthesisJournal of Neurochemistry, 2006
- Rewiring Phagocytic Signal TransductionImmunity, 2006
- Imaging Neuronal Subsets in Transgenic Mice Expressing Multiple Spectral Variants of GFPNeuron, 2000
- Schwann cells degrade myelin and proliferate in the absence of macrophages: evidence fromin vitro studies of Wallerian degenerationJournal of Neurocytology, 1995
- The long-term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotypeImmunity, 1994
- Immunoglobulin gene rearrangement in B cell deficient mice generated by targeted deletion of the JH locusInternational Immunology, 1993
- Axonal modulation of myelin gene expression in the peripheral nerveJournal of Neuroscience Research, 1990
- Wallerian degeneration in the peripheral nervous system: participation of both Schwann cells and macrophages in myelin degradationJournal of Neurocytology, 1989
- Nerve conduction during Wallerian degeneration in the baboonJournal of Neurology, Neurosurgery & Psychiatry, 1972