Journal of Clinical Immunology

, Volume 25, Issue 3, pp 254–264 | Cite as

Axon Reactive B Cells Clonally Expanded in the Cerebrospinal Fluid of Patients with Multiple Sclerosis

  • Yiping Zhang
  • Reng-Rong Da
  • Wenzhong Guo
  • Hui-Min Ren
  • Lutz G. Hilgenberg
  • Raymond A. Sobel
  • Wallace W. Tourtellotte
  • Martin A. Smith
  • Michael Olek
  • Sudhir Gupta
  • Richard T. Robertson
  • Rashed Nagra
  • Stanley Van Den Noort
  • Yufen Qin
Article

Abstract

Demyelination and axonal loss have been described as the histological hallmarks of inflammatory lesions of multiple sclerosis (MS) and are the pathological correlates of persistent disability. However, the immune mechanisms underlying axonal damage in MS remain unknown. Here, we report the use of single chain-variable domain fragments (scFv) from clonally expanded cerebrospinal fluid (CSF) B cells to show the role of an anti-axon immune response in the central nervous system (CNS) in MS. The cellular and subcellular distribution of the antigen(s) recognized by these CSF-derived clonal scFv antibodies (CSFC-scFv Abs) was studied by immunochemical staining of brain tissues obtained at autopsy from patients with MS. Immunochemistry showed specific binding of CSFC-scFv Abs to axons in acute MS lesions. The stained axons showed three major types of axonal pathological changes: 1) linear axons, axonal ovoid formation, and axonal transection were seen in the myelinated white matter adjacent to the lesion; 2) accumulation of axonal ovoid formations and Wallerian degeneration were seen at the border between demyelinated lesions and the adjacent white matter; and 3) Wallerian degeneration occurred at the center and edge of acute demyelinated lesions. These findings suggest a B cell axonal specific immune response in the CNS in MS.

Key Words

CSF B cell clonal expansion CSFC-scFv antibody axonal immunity multiple sclerosis 

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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Yiping Zhang
    • 1
  • Reng-Rong Da
    • 1
  • Wenzhong Guo
    • 1
  • Hui-Min Ren
    • 1
  • Lutz G. Hilgenberg
    • 2
  • Raymond A. Sobel
    • 3
  • Wallace W. Tourtellotte
    • 4
  • Martin A. Smith
    • 2
  • Michael Olek
    • 1
  • Sudhir Gupta
    • 5
  • Richard T. Robertson
    • 2
  • Rashed Nagra
    • 4
  • Stanley Van Den Noort
    • 1
  • Yufen Qin
    • 1
    • 6
  1. 1.Department of NeurologyUniversity of CaliforniaIrvine
  2. 2.Department of Anatomy and NeurobiologyUniversity of CaliforniaIrvine
  3. 3.Department of PathologyStanford University School of MedicineStanford
  4. 4.Neurology Service VA Greater Los Angeles Healthcare System Los Angeles
  5. 5.Department of MedicineUniversity of CaliforniaIrvineCalifornia
  6. 6.Department of NeurologyUniversity of California IrvineIrvine

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