The Immunoglobulin G Heavy Chain Repertoire in Multiple Sclerosis Plaques Is Distinct from the Heavy Chain Repertoire in Peripheral Blood Lymphocytes

Analyses have shown that the repertoire of Ig heavy chain sequences (VH) expressed in multiple sclerosis (MS) plaques or cerebrospinal fluid is consistent with B cell clonal expansion and affinity maturation. PCR amplification of VH sequences from MS lesions obtained from an acute MS patient at autopsy revealed oligoclonal and extensively mutated VH sequences from plaque–periplaque regions with discrete intraclonal differences indicative of B cell clonal expansion in the groups of overrepresented major sequences. None of the VH sequences expressed in plaque regions were detected in peripheral blood lymphocytes from this patient. These data indicate the presence of a CNS-targeted antigen-driven response in MS plaques.