B cell apoptosis in the central nervous system in experimental autoimmune encephalomyelitis: roles of B cell CD95, CD95L and Bcl-2 expression.
The role and fate of B cells in the central nervous system (CNS) in experimental autoimmune encephalomyelitis (EAE) are unknown. Using enzyme-linked immunospot assays we now show that B cells reactive to myelin basic protein (MBP) accumulate in the CNS of Lewis rats with acute EAE induced by immunization with MBP and adjuvants. We also report that B cells are eliminated from the CNS by apoptosis during spontaneous recovery from this disease. Apoptotic B cells were identified by flow cytometry of inflammatory cells extracted from the spinal cord and by histological sections of the spinal cord using light and electron microscopic immunocytochemistry. B cell apoptosis occurred preferentially in the CNS rather than in the peripheral lymphoid organs and was maximal just prior to the onset of spontaneous clinical recovery. Three colour flow cytometry indicated that B cells expressing CD95 (Fas) or CD95 ligand (CD95L) were highly vulnerable to apoptosis, whereas B cells expressing Bcl-2 were relatively protected from apoptosis. We propose that B cells are eliminated from the CNS by the interaction of CD95L and CD95 on the same B cell and that this contributes to the spontaneous resolution of CNS inflammation and clinical recovery in acute EAE.
White
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Neuroimmunology Research Unit, Department of Medicine, The University of Queensland, Clinical Sciences Building, Royal Brisbane Hospital, Brisbane, Queensland, 4029, Australia.
Nguyen
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Pender
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D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology*; D002490:Central Nervous System / Q000166:cytology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000503:physiopathology; D053222:Fas Ligand Protein; D005260:Female; D015151:Immunoblotting; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000276:immunology; D008221:Lymphoid Tissue; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D051381:Rats; D011917:Rats, Inbred Lew; D019014:fas Receptor / Q000096:biosynthesis*
D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D017493:Leukocyte Common Antigens