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Research Article Free access | 10.1172/JCI3568

Clonal expansion and somatic hypermutation of V(H) genes of B cells from cerebrospinal fluid in multiple sclerosis.

Y Qin, P Duquette, Y Zhang, P Talbot, R Poole, and J Antel

Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada. CYYQ@musica.mcgill.ca

Find articles by Qin, Y. in: PubMed | Google Scholar

Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada. CYYQ@musica.mcgill.ca

Find articles by Duquette, P. in: PubMed | Google Scholar

Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada. CYYQ@musica.mcgill.ca

Find articles by Zhang, Y. in: PubMed | Google Scholar

Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada. CYYQ@musica.mcgill.ca

Find articles by Talbot, P. in: PubMed | Google Scholar

Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada. CYYQ@musica.mcgill.ca

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Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada. CYYQ@musica.mcgill.ca

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Published September 1, 1998 - More info

Published in Volume 102, Issue 5 on September 1, 1998
J Clin Invest. 1998;102(5):1045–1050. https://doi.org/10.1172/JCI3568.
© 1998 The American Society for Clinical Investigation
Published September 1, 1998 - Version history
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Abstract

The cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients is characterized by increased concentrations of immunoglobulin (Ig), which on electrophoretic analysis shows restricted heterogeneity (oligoclonal bands). CSF Ig is composed of both serum and intrathecally produced components. To examine the properties of intrathecal antibody-producing B cells, we analyzed Ig heavy-chain variable (V(H)) region genes of B cells recovered from the CSF of 12 MS patients and 15 patients with other neurological diseases (OND). Using a PCR technique, we could detect rearrangements of Ig V(H) genes in all samples. Sequence analysis of complementarity-determining region 3 (CDR3) of rearranged VDJ genes revealed expansion of a dominant clone or clones in 10 of the 12 MS patients. B cell clonal expansion was identified in 3 of 15 OND. The nucleotide sequences of V(H) genes from clonally expanded CSF B cells in MS patients demonstrated the preferential usage of the V(H) IV family. There were numerous somatic mutations, mainly in the CDRs, with a high replacement-to-silent ratio; the mutations were distributed in a way suggesting that these B cells had been positively selected through their antigen receptor. Our results demonstrate that in MS CSF, there is a high frequency of clonally expanded B cells that have properties of postgerminal center memory or antibody-forming lymphocytes.

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