Dataset Information

Investigating the Antigen Specificity of Multiple Sclerosis Central Nervous System-Derived Immunoglobulins.

ABSTRACT: The central nervous system (CNS) of patients with multiple sclerosis (MS) is the site where disease pathology is evident. Damaged CNS tissue is commonly associated with immune cell infiltration. This infiltrate often includes B cells that are found in multiple locations throughout the CNS, including the cerebrospinal fluid (CSF), parenchyma, and the meninges, frequently forming tertiary lymphoid structures in the latter. Several groups, including our own, have shown that B cells from distinct locations within the MS CNS are clonally related and display the characteristics of an antigen-driven response. However, the antigen(s) driving this response have yet to be conclusively defined. To explore the antigen specificity of the MS B cell response, we produced recombinant human immunoglobulin (rIgG) from a series of expanded B cell clones that we isolated from the CNS tissue of six MS brains. The specificity of these MS-derived rIgG and control rIgG derived from non-MS tissues was then examined using multiple methodologies that included testing individual candidate antigens, screening with high-throughput antigen arrays and evaluating binding to CNS-derived cell lines. We report that while several MS-derived rIgG recognized particular antigens, including neurofilament light and a protocadherin isoform, none were unique to MS, as non-MS-derived rIgG used as controls invariably displayed similar binding specificities. We conclude that while MS CNS resident B cells display the characteristics of an antigen-driven B cell response, the antigen(s) driving this response remain at large.

SUBMITTER: Willis SN

PROVIDER: S-EPMC4663633 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Investigating the Antigen Specificity of Multiple Sclerosis Central Nervous System-Derived Immunoglobulins.

Willis Simon N SN Stathopoulos Panos P Chastre Anne A Compton Shannon D SD Hafler David A DA O'Connor Kevin C KC

Frontiers in immunology 20151125

The central nervous system (CNS) of patients with multiple sclerosis (MS) is the site where disease pathology is evident. Damaged CNS tissue is commonly associated with immune cell infiltration. This infiltrate often includes B cells that are found in multiple locations throughout the CNS, including the cerebrospinal fluid (CSF), parenchyma, and the meninges, frequently forming tertiary lymphoid structures in the latter. Several groups, including our own, have shown that B cells from distinct lo ...[more]

PMID: 26648933

Similar Datasets

Project description:Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system (CNS). The persistent inflammation is being mainly attributed to local oxidative stress and inflammasome activation implicated in the ensuing demyelination and axonal damage. Since new control measures remain necessary, we evaluated the preventive and therapeutic potential of a beta-selenium-lactic acid derivative (LAD-?Se), which is a source of organic selenium under development, to control experimental autoimmune encephalomyelitis (EAE) that is an animal model for MS. Two EAE murine models: C57BL/6 and SJL/J immunized with myelin oligodendrocyte glycoprotein and proteolipid protein, respectively, and a model of neurodegeneration induced by LPS in male C57BL/6 mice were used. The preventive potential of LAD-?Se was initially tested in C57BL/6 mice, the chronic MS model, by three different protocols that were started 14 days before or 1 or 7 days after EAE induction and were extended until the acute disease phase. These three procedures were denominated preventive therapy -14 days, 1 day, and 7 days, respectively. LAD-?Se administration significantly controlled clinical EAE development without triggering overt hepatic and renal dysfunction. In addition of a tolerogenic profile in dendritic cells from the mesenteric lymph nodes, LAD-?Se also downregulated cell amount, activation status of macrophages and microglia, NLRP3 (NOD-like receptors) inflammasome activation and other pro-inflammatory parameters in the CNS. The high Se levels found in the CNS suggested that the product crossed the blood-brain barrier having a possible local effect. The hypothesis that LAD-?Se was acting locally was then confirmed by using the LPS-induced neurodegeneration model that also displayed Se accumulation and downmodulation of pro-inflammatory parameters in the CNS. Remarkably, therapy with LAD-?Se soon after the first remitting episode in SJL/J mice, also significantly downmodulated local inflammation and clinical disease severity. This study indicates that LAD-?Se, and possibly other derivatives containing Se, are able to reach the CNS and have the potential to be used as preventive and therapeutic measures in distinct clinical forms of MS.

Dataset Information

Investigating the Antigen Specificity of Multiple Sclerosis Central Nervous System-Derived Immunoglobulins.

Publications

Investigating the Antigen Specificity of Multiple Sclerosis Central Nervous System-Derived Immunoglobulins.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets