The involvement of specific anti myelin basic protein antibody-forming cells in multiple sclerosis immunopathology

Gerritse, Koen; Deen, C.; Fasbender, Marianne; Ravid, Rivka; Boersma, W.J.A.; Claassen, Eric

doi:10.1016/0165-5728(94)90191-0

Cited by 44 publications

(34 citation statements)

References 31 publications

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“…These data suggest that ASC can be retained within the human CNS for prolonged periods in the apparent absence of microbial Ag. However, a confounding issue is the role of self Ag in potentially propagating novel ASC subpopulations during chronic inflammation [23,44]. During JHMV infection, virus-specific T cells decline rapidly as viral replication is controlled and Ag diminishes; nevertheless, T cell retention is prolonged in the continued presence of viral Ag/RNA [39].…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, during acute MS the BBB is compromised, potentially allowing ASC recruitment [21,22]. Only a small portion of the oligoclonal bands in MS CSF are specific for a defined Ag [18, 23,24], while the oligoclonal Ab bands in the CSF of SSPE patients are specific for measles virus [19,20]. These data suggest that B cells are recruited into the CNS during acute peripheral infections with neurological involvement as well as during loss of BBB integrity associated with autoimmunity.…”

Section: Introductionmentioning

confidence: 99%

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CNS viral infection diverts homing of antibody‐secreting cells from lymphoid organs to the CNS

et al. 2006

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Neurotropic coronavirus infection of mice results in acute encephalomyelitis followed by viral persistence. Whereas cellular immunity controls acute infection, humoral immunity regulates central nervous system (CNS) persistence. Maintenance of serum Ab was correlated with tissue distribution of virus-specific Ab-secreting cells (ASC). Although virus-specific ASC declined in cervical lymph node and spleen after infectious virus clearance, virus-specific serum Ab was sustained at steady levels, with a delay in neutralizing Ab. Virus-specific ASC within the CNS peaked rapidly 1 wk after control of infectious virus and were retained throughout chronic infection, consistent with intrathecal Ab synthesis. Surprisingly, frequencies of ASC in the BM remained low and only increased gradually. Nevertheless, virus-specific ASC induced by peripheral infection localized to both spleen and BM. The data suggest that CNS infection provides strong stimuli to recruit ASC into the inflamed tissue through sustained up-regulation of the CXCR3 ligands CXCL9 and CXCL10. Irrespective of Ag deprivation, CNS retention of ASC coincided with elevated BAFF expression and ongoing differentiation of class II + to class II -CD138 + CD19 + plasmablasts. These results confirm the CNS as a major ASCsupporting environment, even after resolution of viral infection and in the absence of chronic ongoing inflammation. IntroductionThe preeminent goal of the immune system is to eliminate pathogens and establish immunological memory [1]. Both T cells and Ab participate in eliminating a variety of pathogens; however, sustained serum Ab is an important criteria for many vaccination strategies, as they provide the first line of defense against re-infection [2]. Upon Ag encounter in regional lymph nodes, B cells undergo clonal expansion in extrafollicular foci and within germinal centers [3,4].Rapidly activated B cells secrete low-affinity Ab but can undergo isotype switching and limited BCR hypermutation as they differentiate into plasmablasts [3]. In the milieu of accessory cells and cytokines, germinal center B cells undergo affinity maturation and ultimately differentiate into both Ab-secreting cells (ASC) and memory B cells. As Ag is depleted, ASC and memory B cells are detected with increasing frequency in BM [2], where both stromal cells and other resident cells provide soluble as well as contact-dependent survival signals, including CXCL12 and BAFF [5]. Ab secretion by terminally differentiated plasma cells is independent of both Ag and T cell regulation [2,6]. Long-lived ASC in BM and spleen maintain serum Ab, thus providing protective immunity to re-infection, sometimes for the [4,6]. In contrast to Ag encountered in the periphery, the regulation of B cell activation by Ag sequestered within the central nervous system (CNS) is less clear. The absence of dedicated lymphatic drainage and the presence of the blood brain barrier (BBB) limits Ag transport from the CNS into secondary lymphoid tissue as well as trafficking of both cells and macromolecule...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CNS viral infection diverts homing of antibody‐secreting cells from lymphoid organs to the CNS

et al. 2006

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“…MBP-specific B cells have been immunolocalized in MS lesions, and local synthesis of MBP-specific autoantibodies in the CNS of MS patients has been demonstrated (17,13). Tissue infiltration by MBP-specific T cells and B cells may be important in the autoimmune response against MBP.…”

Section: Introductionmentioning

confidence: 99%

Recognition of the immunodominant myelin basic protein peptide by autoantibodies and HLA-DR2-restricted T cell clones from multiple sclerosis patients. Identity of key contact residues in the B-cell and T-cell epitopes.

Wucherpfennig¹,

Catz²,

Hausmann³

et al. 1997

J. Clin. Invest.

183

116

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Myelin basic protein (MBP) may be an important autoantigen in multiple sclerosis (MS), with the MBP(82-100) region being immunodominant for T cells and autoantibodies. The structural requirements for autoantibody recognition were compared to those previously defined for MBP-specific T cell clones. MBP autoantibodies were affinity-purified from central nervous system lesions of 11/12 postmortem cases studied. The MBP(83-97) peptide was immunodominant in all 11 cases since it inhibited autoantibody binding to MBP Ͼ 95%. Residues contributing to autoantibody binding were located in a 10-amino acid segment (V86-T95) that also contained the MHC/T cell receptor contact residues of the T cell epitope. In the epitope center, the same residues were important for antibody binding and T cell recognition. Based on the antibody-binding motif, microbial peptides were identified that were bound by purified autoantibodies. Autoantibody binding of microbial peptides required sequence identity at four or five contiguous residues in the epitope center. Microbial peptides previously found to activate T cell clones did not have such obvious homology to MBP since sequence identity was not required at MHC contacts. The similar fine specificity of B cells and T cells may be useful for tolerance induction

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“…Multiple sclerosis (MS) is the most prevalent human demyelinating disease of the CNS (1). The loss of myelin in MS is thought to be autoimmune in nature because it is associated with elevated levels of CD4 ϩ T cells specific for the major myelin proteins (2-4), as well as with the presence of myelin-specific Abs (5,6).…”

mentioning

confidence: 99%

Mechanisms of Immunopathology in Murine Models of Central Nervous System Demyelinating Disease

Ercolini

Miller

2006

The Journal of Immunology

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Many disorders of the CNS, such as multiple sclerosis (MS), are characterized by the loss of the myelin sheath surrounding nerve axons. MS is associated with infiltration of inflammatory cells into the brain and spinal cord, which may be the primary cause of demyelination or which may be induced secondary to axonal damage. Both the innate and adaptive arms of the immune system have been reported to play important roles in myelin destruction. Numerous murine demyelinating models, both virus-induced and/or autoimmune, are available, which reflect the clinical and pathological variability seen in human disease. This review will discuss the immunopathologic mechanisms involved in these demyelinating disease models.

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The involvement of specific anti myelin basic protein antibody-forming cells in multiple sclerosis immunopathology

Cited by 44 publications

References 31 publications

CNS viral infection diverts homing of antibody‐secreting cells from lymphoid organs to the CNS

CNS viral infection diverts homing of antibody‐secreting cells from lymphoid organs to the CNS

Recognition of the immunodominant myelin basic protein peptide by autoantibodies and HLA-DR2-restricted T cell clones from multiple sclerosis patients. Identity of key contact residues in the B-cell and T-cell epitopes.

Mechanisms of Immunopathology in Murine Models of Central Nervous System Demyelinating Disease

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