Intrathecal B-Cell Clonal Expansion, an Early Sign of Humoral Immunity, in the Cerebrospinal Fluid of Patients with Clinically Isolated Syndrome Suggestive of Multiple Sclerosis
| Autor: | Jack P. Antel, Hartmut Wekerle, Yiping Zhang, Pierre J. Talbot, Reng-Rong Da, John Richardson, Neil R. Cashman, Yufen Qin, Wallace W. Tourtellotte, Pierre Duquette, Michael J. Olek, Stanley van den Noort |
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| Rok vydání: | 2003 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Multiple Sclerosis Molecular Sequence Data Immunoglobulin Variable Region Immunoglobulin E Polymerase Chain Reaction Pathology and Forensic Medicine Immune system medicine Humans Amino Acid Sequence Molecular Biology B cell DNA Primers B-Lymphocytes Clinically isolated syndrome Genes Immunoglobulin biology Multiple sclerosis Germinal center Syndrome Cell Biology Middle Aged medicine.disease Clone Cells medicine.anatomical_structure Antibody Formation Mutation Immunology Humoral immunity biology.protein Female Antibody Immunoglobulin Heavy Chains Sequence Alignment |
| Zdroj: | Laboratory Investigation. 83:1081-1088 |
| ISSN: | 0023-6837 |
| Popis: | The development of somatically mutated memory and plasma B cells is a consequence of T cell-dependent antigen-challenged humoral immunity. To investigate the role of B cell-mediated humoral immunity in the initiation and evolution of multiple sclerosis (MS), we analyzed Ig variable heavy chain genes of intrathecal B cells derived from patients with a first clinical manifestation suggestive of MS. Sequences of Ig variable regions showed that B cells in the cerebrospinal fluid from most of these patients were clonally expanded and carried somatic hypermutated variable heavy chain genes. The mutations showed a high replacement-to-silent ratio and were distributed in a way suggesting that these clonally expanded B cells had been positively selected through their antigen receptor. In comparison, intrathecal B-cell clonal expansion often precedes both oligoclonal IgG bands and multiple magnetic resonance imaging lesions. Clinical follow-up study showed that patients with clonally expanded intrathecal B cells had a high rate of conversion to clinically definite MS. The findings provide direct evidence of recruitment of germinal center differentiated B lymphocytes into the central nervous system during the initiation of MS. These results indicate B cell-mediated immune response in the cerebrospinal fluid is an early event of inflammatory reaction in the central nervous system of MS. This procedure also provides a more sensitive method to evaluate the association of humoral immunity in the evolution of MS. |
| Databáze: | OpenAIRE |
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