Contributions
Abstract: P443
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Immunology
A characteristic feature of multiple sclerosis (MS) is the presence of oligoclonal bands in the cerebrospinal fluid (CSF), some of which are restricted to the CSF and not detectable in the blood. In addition, clonally expanded, hypermutated B cells are found in many compartments of the MS brain including the CSF. The presence of ectopic meningeal B cell follicles in late disease suggests a sustained immunopathological B cell response; however the relative contributions of recently recruited peripheral B cells versus locally expanded B cells remains unclear. We investigated the phenotype of
B cells and antibody-secreting cells in the blood and CSF of MS patients using flow cytometry, recruiting patients with a clinically isolated syndrome, relapsing-remitting MS, MS patients ceasing chronic natalizumab (anti-alpha4) treatment and control patients with other neurological diseases. We demonstrated that both B cells and antibody-secreting cells display a more activated phenotype in the CSF versus those in the blood and were more prevalent in MS patients than controls. Antibody-secreting cells in the CSF almost exclusively expressed IgG, compared to the predominant IgA expression seen in the blood, whereas memory B cells displayed similar immunoglobulin expression profiles in both compartments. Furthermore, antibody-secreting cells in the CSF of MS patients demonstrated a higher degree of kappa light chain restriction compared to B cells. These data suggest that in the CSF of MS patients, the majority of B cells result from non-specific inflammatory recruitment of peripheral memory
B cells, whereas antibody-secreting cells are involved in a local and persistent antigen-driven immune response and are more likely to be involved in disease pathogenesis.
Disclosure: This work was funded by the Medical Research Council U.K.
S. John Curnow: Consultant for Celentyx Ltd.
E. Rathbone: nothing to disclose
L. Durant: nothing to disclose
M.R. Douglas: Received funds from Genzyme to attend a conference in 2015
Abstract: P443
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Immunology
A characteristic feature of multiple sclerosis (MS) is the presence of oligoclonal bands in the cerebrospinal fluid (CSF), some of which are restricted to the CSF and not detectable in the blood. In addition, clonally expanded, hypermutated B cells are found in many compartments of the MS brain including the CSF. The presence of ectopic meningeal B cell follicles in late disease suggests a sustained immunopathological B cell response; however the relative contributions of recently recruited peripheral B cells versus locally expanded B cells remains unclear. We investigated the phenotype of
B cells and antibody-secreting cells in the blood and CSF of MS patients using flow cytometry, recruiting patients with a clinically isolated syndrome, relapsing-remitting MS, MS patients ceasing chronic natalizumab (anti-alpha4) treatment and control patients with other neurological diseases. We demonstrated that both B cells and antibody-secreting cells display a more activated phenotype in the CSF versus those in the blood and were more prevalent in MS patients than controls. Antibody-secreting cells in the CSF almost exclusively expressed IgG, compared to the predominant IgA expression seen in the blood, whereas memory B cells displayed similar immunoglobulin expression profiles in both compartments. Furthermore, antibody-secreting cells in the CSF of MS patients demonstrated a higher degree of kappa light chain restriction compared to B cells. These data suggest that in the CSF of MS patients, the majority of B cells result from non-specific inflammatory recruitment of peripheral memory
B cells, whereas antibody-secreting cells are involved in a local and persistent antigen-driven immune response and are more likely to be involved in disease pathogenesis.
Disclosure: This work was funded by the Medical Research Council U.K.
S. John Curnow: Consultant for Celentyx Ltd.
E. Rathbone: nothing to disclose
L. Durant: nothing to disclose
M.R. Douglas: Received funds from Genzyme to attend a conference in 2015