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.
Willis SN, Stathopoulos P, Chastre A, Compton SD, Hafler DA, O’Connor KC. Investigating the Antigen Specificity of Multiple Sclerosis Central Nervous System-Derived Immunoglobulins.Front Immunol. 2015 Nov 25;6:600. eCollection 2015.
So when you have a good idea other people are having it at the same time to exploit technology so you get a series of papers saying the same thing (hopefully), one gets their first and the others cry in their soup at being pipped to the post. These guys have been pipped
So in this post they have taken B cells from MSers brains and then made the antibodies that they can produce and yes they dont react with the myelin. This was seen before. Some respond to neurofilament which maybe a consequence of damage rather than an initial cause. However they find similar specificies in controls so they can’t say what the autoantigen is?. Maybe there is no autoantigen because MS is not an autoimmune disease. However we know that some of these antibodies are pathogenic notably anti-neurofilament antibodies.