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R W Warren

Publications and source records attributed to R W Warren.

At least 37 records · Page 2Linked to original sources
PubMed1984

Specificity analysis of monoclonal anti-DNA antibodies from B6-lpr/lpr mice.

The binding properties of B6-lpr/lpr anti-DNA monoclonal antibodies were characterized to evaluate the influence of genetic background on the diversity and specificity of lpr-induced autoantibody responses. Six anti-DNA antibodies were produced from fusions with B6-lpr/lpr mice, while another was obtained from a fusion with a B6-+/+ mouse immunized with lipopolysaccharide. Each antibody bound single-stranded DNA in preference to double-stranded DNA, with variation of over 300-fold in relative binding activities. In terms of binding to a panel of synthetic polynucleotides, each antibody exhibited a unique antigenic specificity. This binding, however, was not dependent on recognition of a unique base or sugar moiety, since individual antibodies bound polymers of dissimilar composition. These results suggest a diversity of binding reactions for B6-lpr/lpr anti-DNA antibodies, with a clonal repertoire similar to that of mice from autoimmune backgrounds.

Animals↗
PubMed1984

Mechanisms of polyclonal B-cell activation in autoimmune B6-lpr/lpr mice.

The influence of the lpr gene on spontaneous and lipopolysaccharide (LPS)-induced immunoglobulin production was studied in B6 mice homozygous for the mutant lpr gene (B6-lpr/lpr). Male and female mice of this congenic strain were followed for 1 year and sera serially tested by the enzyme-linked immunosorbent assay (ELISA) for the production of antibodies to single-stranded DNA (anti-sDNA), immunoglobulin (anti-IgG), and keyhole limpet hemocyanin (anti-KLH), models of autoantibody and non-autoantibody responses, respectively. Female B6-lpr/lpr mice demonstrated marked spontaneous responses to all three antigens; the responses of male B6-lpr/lpr mice were significantly lower but still exceeded those of the congenic B6-+/+ controls. These results demonstrate a generalized influence of sex on lpr associated responses. To determine whether this sex difference could be demonstrated with other forms of B-cell activation, young B6-+/+ and B6-lpr/lpr male and female mice were immunized with lipopolysaccharide and the induced responses determined. This immunization caused significant increases in the IgM response only. The levels of the induced responses produced after LPS treatment were comparable for +/+ and lpr/lpr mice. These results indicate that the enhanced responsiveness of female mice to lpr action is not reflected in the polyclonal response to LPS, which, furthermore, was unaffected by the presence of lpr. The differential influence of sex on lpr and LPS-induced responses and their apparent independence suggests that lpr and LPS promote B-cell activation by dissimilar mechanisms.

Animals↗
PubMed1984

The influence of the lpr gene on B cell activation: differential antibody expression in lpr congenic mouse strains.

Spontaneous immunoglobulin production in four strains of lpr/lpr congenic mice was investigated to identify genetic interactions in lpr-induced polyclonal B cell activation. Sera were obtained from male and female lpr/lpr mice of the MRL, B6, C3H, and AKR strains as well as controls of +/+ genotypes. Antibody levels were compared at the time of peak response. Quantitative antibody determinations were performed by isotype-specific ELISA assays using responses to single-stranded DNA (sDNA), mouse IgG, rabbit IgG, and keyhole limpet hemocyanin as models. Among the strains studied there were significant differences in the antibody levels observed, with the strain producing highest levels dependent on the response measured. Thus, MRL-lpr/lpr produced the highest levels of IgG anti-sDNA while B6-lpr/lpr mice produced more anti-IgG than mice of other strains. Within each strain, the lpr gene appeared to affect the IgG more than the IgM response. A consistently high response by females was observed only in B6-lpr/lpr mice. These studies suggest that lpr-induced polyclonal B cell activation is influenced by the background genome with the extent of these genetic effects variable among responses.

Animals↗
PubMed1984

Monoclonal rheumatoid factors from B6-lpr/lpr mice.

Monoclonal rheumatoid factors (MoRF) were prepared from autoimmune B6-lpr/lpr mice to investigate the influence of strain background on the specificity of these autoantibodies. Using screening assays for binding to heterologous rabbit IgG, four IgM MoRF were obtained. Three of these antibodies showed a broad pattern of reactivity with IgG antigen, binding BALB/c myeloma IgG1, IgG2a and IgG3 as well as heterologous IgG. One of the antibodies, however, had a distinct form of IgG interaction and was without reactivity with any of the BALB/c myelomas tested. None of the antibodies had significant reactivity with IgG2b. These results suggest common features of B6-lpr/lpr rheumatoid factor (RF) specificities, some of which may be shared by comparable products derived from MRL-lpr/lpr mice. Comparison of these antibodies with those in other reported series suggests that the background genome as well as the nature of the inducing mechanisms may affect the specificity of RF as well as their pathogenetic role.

Animals↗
PubMed1983

Disseminated parainfluenza infection in a child with severe combined immunodeficiency.

An 8-month-old male infant with severe combined immunodeficiency syndrome was admitted to the hospital with pneumonitis and, subsequently, died at 21 months of age. During his lengthy hospitalization, parainfluenza virus type 3 (PIV-3) was isolated from respiratory secretions and unusual sites, such as pericardial fluid, CSF, and WBCs. A postmortem examination showed apparent viral pancreatitis, and PIV-3 was isolated from the lung, brain, and pericardial fluid. To our knowledge, this is the first reported case of disseminated parainfluenza infection identified during life. We speculated that a mutant fusion protein may have been elaborated by the virus, allowing dissemination beyond the respiratory tract.

Brain↗
PubMed1983

Demonstration of abnormalities in expression of thymic epithelial surface antigens in severe cellular immunodeficiency diseases.

Thymic epithelium from three patients with severe cellular immunodeficiency diseases were compared with age-matched normal thymic epithelium using three markers of human thymic epithelium and antibodies against thymosin alpha 1, thymopoietin, and thymosin beta 4. We have previously shown that normal thymic epithelium reacts with antibodies against GQ gangliosides (antibody A2B5) and binds tetanus toxin (TT). In addition, some areas of normal thymic epithelium express human Thy-1 antigen. We found thymic epithelium in patients with severe cellular immunodeficiency diseases to be different from normal subjects. Two children with severe combined immunodeficiency disease (SCID) had thymic epithelium that bound anti-GQ ganglioside antibody but, unlike in normals, did not bind TT. The patient with severe cellular immunodeficiency and normal serum immunoglobulins (Nezelof syndrome) had thymic epithelium that bound TT but, unlike normal thymic epithelium, did not react with anti-GQ ganglioside antibody. Thymic epithelium from both SCID and Nezelof syndrome patients contained thymosin alpha 1, thymopoietin, and thymosin beta 4 and expressed human Thy-1 antigen. In contrast to SCID thymus rudiments, Nezelof thymus contained numerous (though fewer than normal) lymphocytes with mature T cell surface antigens. Thus, using these probes of human thymic epithelium, we have demonstrated heterogeneous defects in thymic epithelial surface marker expression in severe primary cellular immunodeficiency diseases. These defects presumably reflect abnormalities of in vivo thymic epithelial maturation.

Antibodies, Monoclonal↗