Maintenance of B lymphocyte-related clones in the cerebrospinal fluid of multiple sclerosis patients

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 VHDJH segments bearing VH3 and VH4 that were obtained from Cγ 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 VH 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 VHDJH Cγ sequences.