Cloning the antibody response in humans with inflammatory central nervous system disease: analysis of the expressed IgG repertoire in subacute sclerosing panencephalitis brain reveals disease-relevant antibodies that recognize specific measles virus antigens (original) (raw)
1999, Journal of immunology (Baltimore, Md. : 1950)
The presence of increased IgG in the brains of humans with infectious and inflammatory CNS diseases of unknown etiology such as multiple sclerosis may be a clue to the cause of disease. For example, the intrathecally synthesized oligoclonal bands (OGBs) in diseases such as subacute sclerosing panencephalitis (SSPE) or cryptococcal meningitis have been shown to represent Ab directed against the causative agents, measles virus (MV) or Cryptococcus neoformans, respectively. Using SSPE as a model system, we have developed a PCR-based strategy to analyze the repertoire of IgG V region sequences expressed in SSPE brain. We observed abnormal expression of germline V segments, overrepresentation of particular sequences that correspond to the oligoclonal bands, and substantial somatic mutation of most clones from the germline, which, taken together, constitute features of Ag-driven selection in the IgG response. Using the most abundant or most highly mutated gamma H chain and kappa or lambda...
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Conventional and crossed immunoelectrophoresis were used to characterize oligoclonal gamma-globulin bands of the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) or subacute sclerosing panencephalitis (SSPE) or other infections of the central nervous system. Most gamma-globulin bands were identified as IgG, but some bands were identified as kappa or lambda, or both, free light chains, Bands of IgG showed various degrees of light-chain diversity, and individual bands appeared in many instances to be derived from more than one clone of cells. Sequential changes of the oligoclonal IgG were observed in SSPE but not in MS. Oligoclonal IgG was detected in sera from most patients with SSPE and some patients with MS.
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