Maintenance of B lymphocyte-related clones in the cerebrospinal fluid of multiple sclerosis patients |
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Authors: | Colombo Monica Dono Mariella Gazzola Paola Chiorazzi Nicholas Mancardi Gianluigi Ferrarini Manlio |
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Institution: | U.O. Oncologia Medica C, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy. monica.colombo@istge.it |
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Abstract: | A longitudinal study of Ig V gene segments utilized by B cells from the cerebrospinal fluid (CSF) of two patients with multiple sclerosis (MS) was carried out using RT-PCR methodologies. One patient with a relapsing-remitting (RR)-MS was investigated at onset and at relapse, 1 year later. A patient with secondary-progressive (SP)-MS was tested 9 and 13 years after disease onset. Sequence analyses of V(H)DJ(H) segments bearing V(H)3 and V(H)4 that were obtained from Cgamma cDNA genes demonstrated a substantial proportion of shared clones in the samples taken at different times; these clones were identical or closely related, i.e. had the same third complementary determining region (CDR) of the H chain variable region gene (HCDR3) with different mutations in the V(H) segment. Collectively, these data demonstrate that in MS patients there is a strong selective pressure, which could be exerted by antigen (or autoantigen) stimulation, for the maintenance and partial diversification of certain V(H)DJ(H) Cgamma sequences. |
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Keywords: | Multiple sclerosis CSF B lymphocytes Time factor Autoimmunity Gene rearrangement |
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