Maintenance of B lymphocyte-related clones in the cerebrospinal fluid of multiple sclerosis patients.
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.
Colombo
Monica
M
U.O. Oncologia Medica C, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy. monica.colombo@istge.it
Dono
Mariella
M
Gazzola
Paola
P
Chiorazzi
Nicholas
N
Mancardi
Gianluigi
G
Ferrarini
Manlio
M
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D015321:Gene Rearrangement; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics*; D008137:Longitudinal Studies; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000276:immunology*; D013997:Time Factors
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region