Date of Award
1987
Degree Type
Dissertation
Degree Name
Doctor of Philosophy
Abstract
Spontaneous and pokeweed mitogen (PWM) induced anti-nucleic acid antibodies were assayed in cultures of tonsillar and peripheral blood lymphocytes (PBLs) of healthy donors as well as in PBLs from systemic lupus erythematosus (SLE) patients. IgM antibodies (Abs) to single stranded DNA (ssDNA) were detected frequently in PWM cultures of both SLE PBLs (88%) and normal tonsillar lymphocytes (78%). IgM and IgG anti-double stranded DNA Abs were found at high frequencies of 73% and 59% respectively with PWM stimulated SLE PBLs.;Spontaneous production of IgM Abs to ssDNA was identical (44%) in normal tonsillar lymphocytes and PBLs of SLE patients. Human:human hybridomas were generated by fusion of normal tonsillar lymphocytes with GM 4672 cell line. 11.8% of these hybridomas secreted IgM anti-nucleic acid Abs. These monoclonal antibodies (mAbs) reacted with ssDNA, DNA polydG{dollar}\cdot{dollar}polydC, poly-(dA-dT), low molecular weight DNA, RNA and cardiolipin.;Four of the ten mAbs studied reacted with vimentin as well. Anti-idiotypic Ab raised against one of the anti-nucleic acid mAb, was utilized to examine the expression of the corresponding idiotype (ID), 4.6.3, in the panel of hybridoma cell lines as well as in sera of normals and SLE patients. The 4.6.3. ID framework determinant was expressed by a third of all nucleic acid-reactive and non-nucleic acid-reactive mAbs and it was detected in sera from 90% of SLE patients and 24% of normals.;The level of 4.6.3 ID in patients was independent of total serum IgM and IgG and of serum anti-nucleic acid Ab concentrations. These data indicate convincingly that anti-nucleic acid Abs equivalent to those found in SLE patients can be derived from cells of apparently normal individuals. As idiotypes are the serologic markers of immunoglobulin variable region genes, the existence of a common cross-reactive idiotype shared by both normal and SLE lymphocytes, implies that anti-nucleic acid Abs are encoded by common variable region genes present throughout the normal human populations.
Recommended Citation
Cairns, Ewa, "Characterization Of Anti-dna Autoantibody Responses From Lymphoid Cells Of Normal Human Origin" (1987). Digitized Theses. 1589.
https://ir.lib.uwo.ca/digitizedtheses/1589