scholarly journals Evidence For The Involvement of B Cells and Antibody in The Pathogenesis of Multiple Sclerosis in Immunized Mouse With Recombinant Myelin Basic Protein Peptide

Author(s):  
Maryam Sahlolbei ◽  
Maryam Hajizadeh ◽  
Marzie Naseri ◽  
Hossein Ghanbarian ◽  
Seyed Mahmoud Hashemi ◽  
...  

Abstract Over the years, regarding great progresses in knowledge of immunology and neuroscience, the treatment of multiple sclerosis (MS) has been changed. The earlier strategies were focused mainly on T lymphocytes as pioneer cells responsible to inflammatory damage in the central nervous system lesions, whereas B cells, plasma cells and antibodies are also found in the active nerve lesions in MS patients. Despite the accumulating evidence, the role of Myelin basic protein (MBP) antibodies in progression of lesions in nervous system is not completely clear yet. In this regard, here, we present data on B cells and antibody level after MBP immunization of MS mice model. Recombinant fusion protein harboring Myelin basic protein peptide (amino acids 83–99) and CFP was produced in E. coli and purified with chromatography. Then, the C57BL / 6 mice were immunized by rMBP-CFP. Antibody-based assay was used to quantify the level of reactivity to the MBP in mice serum. Subsequently, humoral immunity was analyzed by immunohistochemistry (IHC), ELISA, and Flow cytometry. Our data indicated an increase in autoreactive B cells and MBP specific antibodies after immunization. IHC analysis revealed an increasing penetration rate of immune cells and the nerve lesions development in the nervous system following increasing in MBP antibody titers.This study represented data to support this idea that reactive B cells and antibodies to MBP may contribute to MS pathogenesis. Hence, targeting of these autoreactive B cells and antibodies can be used as potential tools in treatment of MS patients.

Author(s):  
Kostrikina IA ◽  
◽  
Granieri E ◽  
Nevinsky GA ◽  
◽  
...  

Multiple Sclerosis (MS) is known as a chronic demyelinating pathology of the central nervous system. The most accepted MS pathogenesis theory assigns the main role to demyelination of myelin-proteolipid shells due to inflammationrelated with autoimmune reactions. One of the features of MS patients is the enhanced synthesis of oligoclonal IgGs in the bone marrow Cerebrospinal Fluid (CSF). By antigen-specific immunoblotting after isoelectrofocusing of IgGs, oligoclonal IgGs in CSF of MS patients were revealed only against the components of Epstein-Barr virus and Chlamydia. However, there was still unknown to which human auto-antigens in MS patients oligoclonal IgGs may be produced. Here it was first shown that in the CSF of a narrow percentage of MS patients, oligoclonal IgGs are produced against their own antigens: DNA (24% patients), histones (20%), and myelin basic protein (12%). At the same time, the CSF of MS patients contains a very large amount of auto-IgGs-abzymes that hydrolyze DNA, histones, and myelin basic protein, which during isofocusing, are distributed throughout the gel from pH 3 to 10. It is concluded that these multiple IgGs-abzymes, which are dangerous to humans since stimulate development of MS, in the main are non-oligoclonal antibodies.


Autoimmunity ◽  
1991 ◽  
Vol 11 (1) ◽  
pp. 27-34 ◽  
Author(s):  
Zhang Jingwu ◽  
Ying Chin ◽  
Paula Henderikx ◽  
Robert Medaer ◽  
C-H. Chou ◽  
...  

1976 ◽  
Vol 156 (3) ◽  
pp. 627-633 ◽  
Author(s):  
G F Buletza ◽  
M E Smith

Proteolytic activity of central-nervous-system tissue of the normal rat was examined over the pH range 2-9 with casein, haemoglobin and myelin basic protein as substrates. With casein as a substrate, brain and spinal cord homogenates showed very similar activity profiles with increasing pH, with the main peaks of proteolytic activity at pH 3-4 and 5-6. When haemoglobin was used, one broad main peak of activity from pH 3 to 5 was demonstrated. There was no optimum pH, however, for proteolytic activity with myelin basic protein as a substrate, and considerable hydrolysis were observed from pH 3.5 up to pH8. Proteolytic activity at the various pH values was compared by using homogenates of spinal cords from rats with acute experimental allergic encephalomyelitis and those from rats injected with Freund's adjuvant alone. The profiles of activity were similar with peaks at pH 3.5 and 5.5 with casein as a substrate, but the specific activity was significantly higher at most pH values in the spinal-cord homogenates from rats with experimental allergic encephalomyelitis. Similarly the spinal-cord homogenates from these latter rats contained much more proteolytic activity toward myelin basic protein throughout the pH range than was present in the control spinal cords. Homogenates from lymph nodes of rats with experimental allergic encephalomyelitis and from those of the controls contained two to three times as much proteolytic activity as that of the central-nervous-system tissue and had a different proteolytic activity profile form that of the central-nervous system, with higher activity at the neutral than at acid pH. The results are discussed with regard to the probability that inflammatory cells such as lymphocytes may be the cause of the increased proteolytic activity in the central nervous system of animals with experimental allergic encephalomyelitis, and that enzymes from these cells possess the capability of digesting myelin basic protein.


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