Analysis of the fine B cell specificity during the chronic/relapsing course of a multiple sclerosis-like disease in Lewis rats injected with the encephalitogenic myelin oligodendrocyte glycoprotein peptide 35-55.
We have recently shown that a single injection of myelin oligodendrocyte glycoprotein (MOG), or the MOG35-55 peptide, produces a relapsing-remitting neurologic disease with extensive plaque-like demyelination. Given the features that this new autoimmune demyelinating model has in common with the clinicopathologic manifestations of multiple sclerosis, we have examined the Ab reactivity to native MOG and MOG35-55 peptide during the course of the disease in Lewis rats. Following immunization with MOG35-55, varied clinical symptoms were observed; these included hind and foreleg paralysis and various degrees of balance impairment. Disease progression also varied: 3 out of 21 animals had a single mild disease episode; 4 out of 21 had a mild relapsing-remitting disease; and 14 out of 21 had severe relapsing-remitting disease. Ab reactivity to MOG35-55 and native MOG was first detected in all rats 4 wk postimmunization and persisted throughout the 12 wk of observation. The Ab response was highly restricted with no reactivity to other peptides encompassing different extracellular segments of MOG. Fine epitope mapping showed that Ab from serum and cerebrospinal fluid of injected rats reacted strongly to MOG37-46 and to a lesser extent to MOG43-50. Although significant levels of anti-MOG Abs appeared necessary for the development of demyelinating lesions, their presence in blood and cerebrospinal fluid alone was not sufficient to produce severe clinical symptoms. These results demonstrate that the MOG35-55 peptide is highly encephalitogenic and can induce strong T and B cell responses. It is probably the complex interaction between these T and B cells that determines the severity of disease in individual rats.
Ichikawa
M
M
Neuroimmunology Laboratory, La Trobe University, Melbourne, Victoria, Australia.
Johns
T G
TG
Liu
J
J
Bernard
C C
CC
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002908:Chronic Disease; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology*; D000939:Epitopes / Q000134:cerebrospinal fluid / Q000276:immunology*; D006614:Hindlimb; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007106:Immune Sera / Q000032:analysis; D007267:Injections; D008297:Male; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000276:immunology*; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000008:administration & dosage / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D009836:Oligodendroglia / Q000276:immunology*; D010455:Peptides / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D012008:Recurrence
D000939:Epitopes; D007106:Immune Sera; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010455:Peptides