Neuron-binding human monoclonal antibodies support central nervous system neurite extension

Arthur E. Warrington, Allan J. Bieber, Virginia Van Keulen, Bogoljub Ciric, Larry R. Pease, Moses Rodriguez

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Two human IgMs (sHIgM12 and sHIgM42) were identified that supported in vitro central nervous system (CNS) neurite extension equal to the potent neurite stimulatory molecule laminin. Both IgMs bound to multiple cell types in unfixed CNS tissue and to the surface of neurons in culture. Both monoclonal antibodies (mAbs) overrode the inhibitory effect of CNS mouse myelin on granule cell neurite extension. Neither mAb bound to the surface of mature oligodendrocytes or strictly colocalized with myelin proteins. Sialidase treatment eliminated the neuronal surface binding of both mAbs, whereas blocking sphingolipid synthesis with Fumonisin B, or removing GP1-linked proteins with PIPLC did not. When used as substrates for mixed neuron/glia aggregates, sHIgM12 and sHIgM42 supported robust neurite extension while astrocytes remained in the aggregates. In contrast, laminin supported astrocyte migration and spreading. Human mAbs that support neurite extension are novel factors that may be of use in encouraging axon repair following injury while minimizing glial cell infiltration. Both human mAbs were isolated from individuals with monoclonal gammopathy. Each individual has carried high mAb titers in circulation for years without detriment. sHIgM12 and sHIgM42 are therefore unlikely to be systemically pathogenic.

Original languageEnglish (US)
Pages (from-to)461-473
Number of pages13
JournalJournal of Neuropathology and Experimental Neurology
Volume63
Issue number5
DOIs
StatePublished - May 2004

Keywords

  • Cerebellar granule cell
  • Human monoclonal antibody
  • Laminin
  • Monoclonal gammopathy
  • Myelin
  • Neurite extension
  • Sialic acid

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Neuron-binding human monoclonal antibodies support central nervous system neurite extension'. Together they form a unique fingerprint.

  • Cite this