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) ex pressed in multiple sclerosis (MS) plaques or cerebrospinal fluid is consis tent with B cell clonal expansion and affinity maturation. PCR amplificatio n of VH sequences from RIS lesions obtained from an acute MS patient at aut opsy revealed oligoclonal and extensively mutated VH sequences from plaque- periplaque regions with discrete intraclonal differences indicative of B ce ll 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. (C) 2000 Academic Pres s.