Investigation of the adaptive immune response in multiple sclerosis

Rathbone, Emma (2018). Investigation of the adaptive immune response in multiple sclerosis. University of Birmingham. Ph.D.

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Abstract

In multiple sclerosis (MS), clonally-expanded brain-resident B cells may sustain chronic disease, however their relative contributions versus recently recruited B cells is unclear. Furthermore, pro-inflammatory CD20+ T cells may also be involved in MS pathogenesis. This study aimed to characterise the cerebrospinal fluid (CSF) B cell response in MS and investigate the features of CD20+ T cells.

CSF B cells and antibody-secreting cells (ASC) displayed an activated phenotype and were identified in MS CSF at a higher frequency than controls. In contrast to the periphery, CSF ASC almost exclusively expressed IgG and were strongly lgK-biased, whereas memory B cells displayed similar immunoglobulin expression profiles in both compartments. MS CSF antibodies were frequently reactive towards EBNA-1, which preferentially induced an lgK-biased antibody response. Finally, CD20+ T cells displayed a highly activated effector phenotype and were present in the CSF, although their frequencies were no different between MS and OND groups.

These findings suggest that most CSF B cells result from non-specific recruitment, whereas ASC are involved in a persistent lgK-biased antigen-driven immune response, which may primarily be directed towards EBNA-1. Despite their highly activated phenotype, a role for CD20+ T cells in MS pathogenesis, if any, remains to be determined.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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