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H Borel

Publications and source records attributed to H Borel.

53 records · Page 3Linked to original sources

Immune response to nucleic acid antigens and native DNA by human peripheral blood lymphocytes in vitro.

The immunogenicity of DNA fragments (either oligonucleotide (oligo) or total DNA digest) covalently linked to keyhole limpet hemocyanin (oligo-KLH or DNA-KLH) was tested with peripheral blood lymphocytes (PBL) from 63 systemic lupus erythematosus patients (SLE) in vitro. PBL from 10 normal individuals and 11 rheumatoid arthritis (RA) patients served as controls. Antibodies to three nucleic acid antigens (oligo, denatured DNA (d-DNA), and native DNA (n-DNA] were assayed in supernatants of cultured lymphoid cells by a sensitive solid-phase radioimmunoassay. More than 50% of SLE and RA patient lymphoid cells formed spontaneous antibodies to one or several nucleic acid antigens. In contrast, only two normals did. After in vitro challenge with oligo-KLH or DNA-KLH, cultured lymphocytes of more than 50% of SLE patients formed antibodies to one or several nucleic acid antigens. Similar results were obtained in PBL from RA patients. In SLE patients, the response to both antigens was either monospecific or polyspecific, but DNA-KLH appeared to raise a greater proportion of antibody to n-DNA than oligo-KLH. A greater proportion of patients with active disease responded in vitro compared with those with inactive disease. A mixture of oligo together with KLH was not immunogenic in vitro. Oligo-KLH or DNA-KLH did not raise antibody to an irrelevant antigen, ovalbumin. Of particular interest, PBL from seven of 10 normal subjects formed antibody to n-DNA after challenge in vitro with oligo-KLH. The data support the view that DNA fragments could be an important immunogen in SLE. Furthermore, this study provides an in vitro model to test the tolerogenicity of similar fragments of DNA linked to self carrier molecules such as gamma-globulin.

Antibody Formation↗

Conjugation of DNA fragments to protein carriers by glutaraldehyde: immunogenicity of oligonucleotide-hemocyanin conjugates.

The practical realization of the concept of specific immunotherapy for systemic lupus erythematosus (SLE) has been hampered, thus far, by an inability to link DNA fragments to carrier protein. In this paper, a novel technique is described, in which glutaraldehyde is the linking agent. A 2-stage method was used to link oligonucleotides to a soluble protein carrier, such as keyhole limpet hemocyanin (KLH) or human gamma globulin (HGG), whereas a 1-stage technique was sufficient to link oligonucleotides to sheep red cells. Both the ultraviolet absorbance spectrum and diphenylamine assay demonstrated that oligonucleotides were coupled to soluble protein. The conjugate of oligonucleotide to protein carrier appears to be recognized by anti-DNA antibody since oligonucleotide linked to either KLH or HGG inhibited the binding of anti-DNA antibody in vitro, and oligonucleotide-coupled sheep cells are agglutinating by seropositve sera from lupus patients. In addition, oligonucleotide-KLH raised hemagglutinating antibody to denatured DNA in C57BL/6, DBA/2 or NZB mice, as well as IgG antibody as detected by SPRIA in C57BL/6 and DBA/2 mice. The significance of this new method for the development of an antigen specific therapy of SLE is discussed.

Aldehydes↗

Influence of intravenous administration of nucleoside-coupled spleen cells on murine lupus nephritis in female (NZB X NZW)F1 mice.

In this study, we examine the influence of the intravenous administration of nucleoside-coupled spleen cells on the spontaneous development of murine lupus nephritis in young and adult BWF1 mice. In both age groups, this treatment failed to affect the autoimmune disease. Rather, in young mice administration of nucleoside-coupled spleen cells accelerates the appearance of anti-DNA antibody suggesting that BWF1 have a specific defect in the immunoregulation of anti-DNA antibody production. The significance of this finding for the pathogenesis of the disease in BWF1 mice is discussed.

Animals↗

Detection of antibody-forming cells and humoral antibody to horseradish peroxidase.

Two new simple methods for detecting antibody-forming cells by hemolytic plaque assay and hemagglutinating antibody to horseradish peroxidase have been developed in mice. Both techniques utilize as target, sheep erythrocytes coupled directly with horseradish peroxidase. These assays are sensitive, antigen-specific and are useful to quantitate both direct and indirect antibody-forming cells and humoral antibodies.

Animals↗

Carrier determined tolerance with various subclasses of murine myeloma IgG.

Groups of BALB/c mice were treated with various conjugates of 2,4 dinitrophenyl (DNP) and BALB/c myeloma proteins belonging to the four subclasses of IgG (IgG1, IgG2, IgG2b, IgG3). Immediately therafter, they were challenged with DNP-keyhole limpet hemocyanin in complete Freund's adjuvant and antibody to the hapten was measured by direct and indirect hemolytic plaque assay. The results show that all subclasses of IgG are effective as tolerance-inducing carriers. However, the ability of induce tolerance is dependent upon the concentration of hapten bound to each myeloma protein. Tolerogenic conjugates suppress both direct and indirect plaque-forming cells in all types of antibodies measured (IgG1, IgG2a, IgG2b, IgGa), whereas, non-tolerogenic conjugate failed to suppress them. The intact molecule of IgG but not its fragments (Fab, F(ab)2', Fc) appear necessary as tolerance-inducing carriers. It is suggested that the ability to induce tolerance is related to the capacity of the tolerogenic conjugates to cause receptor blockade.

Animals↗

Food allergens transformed into tolerogens.

Antigen presentation determines immunologic outcome, and by modifying the presentation of allergen to the host one can prevent an allergic response. Under certain conditions, covalent linkage, of ovalbumin to rat IgG, a molecule already tolerated by the host, can make a protein-IgG conjugate which down-regulates the immune response to this food allergen. The suppression is allergen specific. It affects both T and B cell immune responses. Administration of allergens linked to isologous IgG may provide a novel strategy for allergy prevention.

Allergens↗