Axon reactive B cells clonally expanded in the cerebrospinal fluid of patients with multiple sclerosis.
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.
Zhang
Yiping
Y
Department of Neurology, University of California, Irvine, California 92697-4275, USA.
Da
Reng-Rong
RR
Guo
Wenzhong
W
Ren
Hui-Min
HM
Hilgenberg
Lutz G
LG
Sobel
Raymond A
RA
Tourtellotte
Wallace W
WW
Smith
Martin A
MA
Olek
Michael
M
Gupta
Sudhir
S
Robertson
Richard T
RT
Nagra
Rashed
R
Van Den Noort
Stanley
S
Qin
Yufen
Y
D000941:Antigens / Q000032:analysis; D001369:Axons / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D001921:Brain / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation; D002555:Cerebrospinal Fluid / Q000166:cytology*; D002999:Clone Cells / Q000276:immunology; D006801:Humans; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region / Q000276:immunology; D007150:Immunohistochemistry; D009103:Multiple Sclerosis / Q000209:etiology / Q000276:immunology*; D014855:Wallerian Degeneration
D000941:Antigens; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region