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Biomedical subjects

A Blancher

Publications and source records attributed to A Blancher.

At least 19 recordsLinked to original sources
PubMed1992

Diversity of human anti-D monoclonal antibodies revealed by reactions with chimpanzee red blood cells.

Fifty-three human anti-D monoclonal antibodies (mAbs) revealed a striking diversity of reactions in tests with panels of chimpanzee red blood cells (RBCs) of various R-C-E-F blood group phenotypes (counterparts of the human Rh-Hr groups). The reactivities of these antibodies, which depended on the agglutination technique used, could be classified into four main types. These patterns of reactivity of anti-D mAbs with chimpanzee RBCs showed only limited correlation with types of reactions observed with human D variant RBCs. Primate red cells may, therefore, constitute an independent test system for subclassification of human monoclonal antibodies. Comparison of reactivities of human anti-D mAbs with chimpanzee and human D variant RBCs confirms the homology between the chimpanzee Rc, and the human D antigens. The chimpanzee Rc shares with human D the epitopes epD5, epD6/7 and epD8, but lacks epitopes epD1, epD2, epD3 and epD4 of the Rh mosaic, thus resembling the human D variants IVb and Vc.

Animals↗
PubMed1992

Survival of human monoclonal anti-Rho (D) antibodies in the rhesus monkey.

In vivo half-life of a 125I-labeled human anti-D monoclonal antibody (mAb) and that of 131I-labeled Rho-GAM was assessed in a rhesus monkey injected simultaneously with both reagents. The half-life of the mAb was 7.9 days, compared to 17 days of Rho-GAM. Survival of the second dose of mAb, given 34 days after the first injection, was identical to that of the first dose, thus showing that the human mAb did not elicit an immune response. The in vitro produced human mAbs appear to be an alternative, unlimited source of anti-D antibodies for possible use in prevention of feto-maternal Rh immunization.

Animals↗
PubMed1992

[Study of equivalents of rhesus antigens in non-human primates].

Human alloantibodies specific of some Rh antigens cross-react with non human primates red blood cells. These crossreactions demonstrated that only African apes express equivalents of Rho (D) and hr' (c). The antigenic resemblance between these two human antigens and their primate homologues is confirmed by the reactivities of human anti-D and anti-c monoclonal antibodies. The use of a human Rh cDNA probe allowed to confirm by Southern blot hybridization that nonhuman primates possess Rh-like genes. The number of Rh-like genes per haploid genome was deduced from the results obtained with exon-specific probes.

Animals↗
PubMed1991

Antibody BNH9 detects red blood cell-related antigens on anaplastic large cell (CD30+) lymphomas.

Two new monoclonal antibodies--BNH9 and BNF13--were generated by using a human lung adenocarcinoma cell line and standard hybridoma techniques. Both were found to react with epithelial and endothelial cells in routinely fixed and embedded tissues. Unexpected membrane labelling of some large cell lymphomas while non-reacting with normal lymphoid cells, prompted further characterisation. The antibodies were found to recognise red blood cell-related oligosaccharide antigens. The specificities were directed towards H and Y determinants. A distinctive pattern of reactivity was found for BNH9 in studying 480 cases of various lymphoid neoplasms. Strong expression of H and/or Y antigens was observed in 65/127 (51%) cases of anaplastic large cell(ALC) (CD30+) lymphomas, which are also known to co-express epithelial membrane antigen (EMA) frequently. Only a minority (less than 6%) of other non-Hodgkin's lymphomas (NHL) (CD30-,EMA-; 208 cases) and Hodgkin's disease (HD) (CD30+, EMA-; 126 cases) were positive. Expression of H and Y antigens was inducible on normal lymphocytes by mitogenic stimulation and by Epstein-Barr virus infection. The data suggest remarkable biological differences of ALC lymphomas within NHL and from HD.

Antibodies, Monoclonal↗
PubMed1991

Polyreactivity of human monoclonal antibodies: human anti-Rh monoclonal antibodies of IgM isotype are frequently polyreactive.

The specific aim of this study was to characterize human anti-Rh monoclonal antibodies cross-reacting with self-antigens. We studied supernatants from man-mouse hybridomas and from lymphoblastoid cell lines. Man-mouse hybridomas were established by fusion of peripheral blood lymphocytes from healthy individuals recently immunized against Rh alloantigens, with mouse myeloma (or man-mouse heteromyeloma) cell lines. Lymphoblastoid cell lines were produced by Epstein-Barr virus induction of lymphocytes from identical sources. Of the 55 monoclonal alloantibodies studied, 11 also reacted with intracellular self-antigens as demonstrated by immunofluorescence assay on cryostat sections of human tissues. This cross-reactivity was mainly a property of monoclonal alloantibodies belonging to the IgM isotype (among the 11 cross-reacting mAbs 10 were IgM). The cross-reactivities of these monoclonal antibodies were ascertained by absorption of alloreacting antibodies with red blood cells. Similar results were obtained on a panel of purified cellular antigens by ELISA. The results confirm that during an immune response against a foreign antigen (alloantigen), B cells that produce polyreactive antibodies are not excluded from the pool of responding cells. Therefore, polyreactive autoantibodies present in sera from healthy individuals may be the result of an immune response against foreign antigens.

Antibodies, Monoclonal↗
PubMed1991

Anti-human red cell monoclonal antibodies produced by macaque-mouse heterohybridomas.

Eight monoclonal antibodies (Mabs) against human red cells were produced by macaque-mouse heterohybridomas. All Mabs uniformly reacted with all human red blood cells tested, but only some agglutinated the red cells of anthropoid apes occasionally detecting intraspecies polymorphisms. None was reactive with blood of Old and New World monkeys. One of the Mabs recognized the Vc antigen of the chimpanzee V-A-B-D system, the homologue of the human M-N blood group system.

Animals↗
PubMed1990

Definition of the human immunoglobulin variable lambda (IGLV) gene subgroups.

Comparison of 60 human immunoglobulin variable lambda (IGLV) sequences allowed us to define seven subgroups designated V lambda I to V lambda VII. We demonstrate that all lambda proteins sequenced so far fall into the subgroups I, II, III and VI, and that the lambda regions previously assigned to subgroups IV and V belong, in fact, to subgroups III and II, respectively. Four sequences not belonging to any of the subgroups I, II, III and VI define the new subgroups IV, V and VII. Interestingly, these subgroups show a higher homology to rabbit or mouse V lambda genes than to the other human V lambda subgroups. By comparison of the proteins either with the sequences deduced from the germ-line genes or with the consensus sequences, the rate of amino acid changes due to somatic mutations or allelic variations was evaluated in several lambda proteins. Framework and complementarity-determining regions of the human IGLV genes and proteins were delineated. Alignment of the lambda sequences shows that functional V-J rearrangement occurs, with or without deletion of nucleotides encoding one or two amino acids at the 3' end of the V gene. Diversity of the third complementarity-determining region is due to somatic mutations and to flexible V-J junction, but there is no evidence of N-diversity in the human lambda locus.

Alleles↗
PubMed1989

Heterogeneity in the ability of IgG1 monoclonal anti-D to promote lymphocyte-mediated red cell lysis.

Thirty-four IgG anti-D human monoclonal antibodies (mAb) derived from 18 donor were assessed for their ability to mediate lysis of D+ red cells by lymphocytes in antibody-dependent cell-mediated cytotoxicity assays. Cell-bound antibody was quantified and the mAb were compared at similar levels of sensitization. The majority (23/31) of IgG1 and all (3/3) IgG3 mAb were ineffective; two donors produced both lytic and non-lytic anti-D mAb. Greater sensitivity was achieved using fluid-phase antibody (as culture supernatants) in the assay than was obtained with pre-sensitized red cells. Minimum levels of 2000 anti-D molecules per cell were required for lysis using pre-sensitized cells. Partial D red cells (DIVa, DVa and DVI) were lysed by three mAb that were lytic with normal D+ cells. There was no relationship between lytic ability and Gm allotype or D epitope specificity of the antibodies. Four mAb to other blood group specificities were tested: two (anti-E and anti-G) were lytic and two (anti-c and anti-Kell) were not lytic. Possible reasons for the heterogeneity of the lytic activity by the mAb are discussed.

Antibodies, Monoclonal↗
PubMed1989

Interferons and multiple sclerosis.

Interferons (IFNs) are a family of proteins with antiviral, antitumoral and immunomodulating properties. Multiple Sclerosis (MS) is a CNS disease in which the immune reaction (IR) is the cause of the inflammatory demyelinating lesions. IFNs have been demonstrated in active lesions. The location of IFN gamma on astrocytes suggests an enhancing activity on IR by inducing Ia antigen expression on these cells. In contrast, IFN alpha/beta located on microglial cells and astrocytes might limit the growing lesion. MS patients frequently present a defective response of NK cell activity and an abnormally low production of IFNs reflecting immune dysregulation. The therapeutic trials available to date are discussed: IFN gamma possesses a severe deleterious effect but IFN alpha/beta are still under consideration due to a possible beneficial activity.

Humans↗
PubMed1989

Natural autoantibodies in nude and normal outbred (Swiss) and inbred (BALB/c) mice.

Spleen cells from adult unprimed outbred (Swiss) and inbred (BALB/c) mice, either normal (no) or athymic-nude (nu) as well as spleen cells from Swiss nude mice bearing two different human tumors (BUR and PINQ), were fused with the mouse non-secreting myeloma cell line P3X63 Ag8-653. The supernatants of immunoglobulin secreting hybrids, all containing IgM, were screened for antibody activity against macromolecular antigens (autologous: actin, tubulin, myosin, dsDNA) and haptens (TNP, NP, NIP and NBrP). Furthermore, their idiotypic determinants were analyzed using a rabbit anti-idiotype which recognizes a major cross-reactive idiotype (IdD23) of BALB/c natural polyreactive autoantibodies. In all the mice studied, we identified: (1) hybrids reacting strongly with one or more haptens (10.7 to 37.8%) and (2) hybrids secreting natural monoclonal autoantibodies (NMoAb) with broad reactivities (polyreactive and/or oligoreactive) against autoantigens and/or haptens (11.4 to 26.8%). The results indicate that: (1) cells secreting natural autoantibodies with broad reactivities exist in both normal and nude mice, independently of the genetic background (inbred/outbred) of the mouse. However, in nude mice, the natural autoantibodies exhibit a more restricted pattern of reactivity (oligoreactive) compared to those of normal mice, and do not express the common idiotype IdD23 of natural polyreactive autoantibodies. (2) Tumors grafted into nude mice seem to induce the expression of polyreactive autoantibodies bearing the IdD23.

Animals↗
PubMed1989

Human monoclonal autoantibodies produced by hybridomas derived from lymphocytes of multiple sclerosis patients.

The aim of this study was to characterize autoantibodies produced in vitro by peripheral blood lymphocytes (PBL) of patients affected with multiple sclerosis (MS). We studied supernatants from man-mouse hybridomas established by fusion of PBL from 6 MS patients (group I) and from 13 individuals free of any neurological pathology (group II) with the mouse myeloma cell line P3X63 Ag8-653. They were screened for human IgG or IgM production by ELISA. Autoantibody activity against lymphocytes was studied by cell-binding ELISA. Anti-tissue reactivity was assessed by indirect immunofluorescence assay (IFA) on human cerebellum and peripheral nerve as well as on a panel of 8 non-nervous tissues. Additional ELISA tests were performed on 4 purified cellular antigens. Among 522 supernatants in group I, 13.7% contained Ig, mainly IgM, as compared to 25% among 1212 supernatants in group II; 8.3% in group I and 6.7% in group II contained anti-tissue autoantibodies. Antibodies against purified cellular antigens were found in 6% of the supernatants in group II versus 7% in group II. One human monoclonal anti-astrocyte antibody from group I was further studied. This IgM lambda (SAN-7) was particularly polyreactive and recognized glial fibrillar acid protein and other intermediate filaments, as well as tubulin and myosin. Moreover, cross-reactivity was observed with a hapten (TNP-BSA).

Antibodies, Monoclonal↗
PubMed1989

Characterization of an IgG2, G2m(23) anti-Rh-D antibody.

IgG2, G2m(23) anti-Rh-D antibodies were detected in the serum of a donor. It has been characterized by Gm typing and the use of polyclonal and mouse monoclonal anti-IgG subclasses (which had proved to be satisfactory for agglutination of sensitized red blood cells). This anti-D constitutes a good reagent for G2m(23) typing.

Antibodies, Monoclonal↗
PubMed1987

Production of monoclonal antibodies using spleen cells from nude mice bearing human tumors.

Monoclonal antibodies were generated with spleen cells from nude mice bearing human tumors. Three grafted tumors were selected because of their difference in metastatic ability in nude mice. Two were non-metastasizing carcinomas and one a highly metastasizing adenocarcinoma of the lung (Bur-tumor). Two normal nude mice were used as controls. Culture supernatants were screened by immunoperoxidase using frozen sections from both the immunizing human tumor and normal human tonsil to detect unexpected monoclonal antibodies. Two kinds of monoclonal antibodies were obtained. The first were directed against miscellaneous membrane and/or cytoplasmic antigens expressed by normal cells (e.g. normal tonsillar epithelium). Most of these antibodies corresponded to auto-antibodies and their frequency did not appear to be influenced by the fact that the mice were with or without grafted human tumors. The second type of antibodies were directed against tumor-associated antigen and generated only by fusing splenocytes from nude mice bearing the metastasizing lung adenocarcinoma. On frozen sections Bur-1-anti-tumor antibody stained all but one lung carcinoma. Occasional carcinomas originating from other organs such as pancreas and breast were also labelled. On the other hand, more than half of the cases of so-called "malignant histiocytosis" (Ki-1 lymphoma) seemed to express this epithelial antigen. Some normal cells in the lung, pancreas (acini), and kidney (distal tubules) also bound Bur-1 antibody. These results suggested that Bur-1 antibody could be related to some antibodies already described, directed against epithelial membrane antigens. When Bur-tumor was analysed by immunoblotting with Bur-1 antibody a positive reaction was obtained with material migrating in the kD-45kD molecular-weight region.

Adenocarcinoma↗