Heightened B lymphocyte (B-cell) activity within the central nervous system (CNS) as manifested by increased CNS and cerebrospinal fluid (CSF) immunoglobulin (Ig) levels, frequently in an oligoclonal pattern, is the most common immunologic abnormality in patients with multiple sclerosis (MS). The antigenic specificity for much of this Ig has not been determined. The nature of the abnormality of immunoregulation responsible for this abnormal CNS B-cell activity is not known. We will examine CSF and extracts of plaque, periplaque and normal-appearing white matter from MS brains for the presence of two lymphokines known to nonspecifically (non-antigen specific) stimulate B-cells: B-cell growth factor (BCGF) and B-cell differentiation factor (BCDF). BCGF activity will be assayed by measuring incorporation of tritiated thymidine (3H-Tdr) by purified peripheral blood B-cells in the presence of anti-Mu antibodies. BCDF activity will be tested for by determining stimulation of immunoglobulin secreting cells (IgSC) in 2 assays: a) the staphylococcal aureus Cowan (SAC) co-stimulation assay on purified peripheral blood B-cells; and, b) the GM 1500 B-cell line. We will obtain lymphocytes from different plaques from MS patients and culture these cells in vitro. We will: a) measure the amount of Ig secreted by these cells; and, b) compare the spectrotype (oligoclonal) pattern of Ig secreted by these cells with that of Ig obtained from the same plaque. Increased knowledge of the mechanisms underlying the altered Ig secretion in the CNS will increase our understanding of immunologic abnormalities in MS and may further elucidate the connection between these alterations and the pathogenesis of MS.