期刊
SCIENCE TRANSLATIONAL MEDICINE
卷 6, 期 248, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.3008930
关键词
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资金
- National Multiple Sclerosis Society [RG-4868]
- NIH/National Institute of Neurological Disorders and Stroke [K02NS072288]
- Pfizer Inc.
- Rachleff Family Foundation
In multiple sclerosis (MS), lymphocyte-in particular B cell-transit between the central nervous system (CNS) and periphery may contribute to the maintenance of active disease. Clonally related B cells exist in the cerebrospinal fluid (CSF) and peripheral blood (PB) of MS patients; however, it remains unclear which subpopulations of the highly diverse peripheral B cell compartment share antigen specificity with intrathecal B cell repertoires and whether their antigen stimulation occurs on both sides of the blood-brain barrier. To address these questions, we combined flow cytometric sorting of PB B cell subsets with deep immune repertoire sequencing of CSF and PB B cells. Immunoglobulin (IgM and IgG) heavy chain variable (V-H) region repertoires of five PB B cell subsets from MS patients were compared with their CSF Ig-V-H transcriptomes. In six of eight patients, we identified peripheral CD27(+)IgD(-)memory B cells, CD27(hi)CD38(hi) plasma cells/plasmablasts, or CD27(-)IgD(-) B cells that had an immune connection to the CNS compartment. Pinpointing Ig class-switched B cells as key component of the immune axis thought to contribute to ongoing MS disease activity strengthens the rationale of current B cell-targeting therapeutic strategies and may lead to more targeted approaches.
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