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Accumulation of Clonally Related B Lymphocytes in the Cerebrospinal Fluid of Multiple Sclerosis Patients
| Content Provider | Scilit |
|---|---|
| Author | Colombo, Monica Dono, Mariella Gazzola, Paola Roncella, Silvio Valetto, Angelo Chiorazzi, Nicholas Mancardi, Giovanni L. Ferrarini, Manlio |
| Copyright Year | 2000 |
| Description | The accumulation of B lymphocyte clones in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) and patients with other neurological disorders was investigated using PCR technologies. Oligoclonal B cell accumulations were detected in 10 of 10 MS patients, but only in 3 of 10 of the patients with other neurological disorders. Analyses of the Ig V(D)J sequences on the CSF from MS patients disclosed that $V_{H}$3 and $V_{H}$4 genes were extensively mutated compared with germline sequences. Moreover, a substantial proportion of the molecular clones analyzed shared the same third CDR of the H chain variable region gene (HCDR3) and the same $V_{H}$ genes, albeit with different numbers and locations of point mutations, thus indicating an ongoing process of intraclonal diversification. A larger number of clonally related $V_{H}$ sequences could be obtained by using a $V_{H}$3 gene-specific PCR so that genealogical trees depicting the process of diversification could be drawn. Analyses of the Ig V(D)J from the CSF of a patient with viral meningitis and oligoclonal B cell accumulations revealed that $V_{H}$3 genes were extensively mutated. However, no intraclonal diversification could be observed even using $V_{H}$3 gene-specific PCR methodologies. Clone-specific PCR and sequencing was used to detect the V(D)J found in the CSF of one MS patient in the PBL of the same patient. Only 1/3 of the V(D)J sequences investigated could be demonstrated in the PBL, indicating that the V(D)J genes utilized by B cells in the CSF are much less represented in the PBL. Collectively, the data suggest that in MS there is a compartmentalized clonal expansion. |
| Ending Page | 2789 |
| Page Count | 8 |
| Starting Page | 2782 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.164.5.2782 |
| Alternate Webpage(s) | http://www.jimmunol.org/content/164/5/2782.full.pdf |
| Journal | The Journal of Immunology |
| Issue Number | 5 |
| Volume Number | 164 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2000-03-01 |
| Access Restriction | Open |
| Subject Keyword | Ms Patients |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
