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Biomedical subjects

A Blancher

Publications and source records attributed to A Blancher.

At least 73 records · Page 4Linked to original sources
PubMed1993

Human monoclonal anti-D-induced clearance of human D-positive red cells in a chimpanzee model.

Two human monoclonal anti-Rh0(D) antibodies, one IgG1, and one IgG3, were tested for their ability to clear human D-positive red blood cells (RBCs) from chimpanzee circulation. Human RBCs (phenotype A1, R1r) from 1 donor were radiolabelled with chromium 51 and injected into 4 chimpanzees. One day later the control animal received isotonic saline whereas 2 animals received 400 micrograms of purified human monoclonal anti-D, either IgG1 or IgG3. The remaining animal received both antibodies together (200 micrograms of IgG1 and 200 micrograms of IgG3). Both individual antibody-mediated clearance of human D-positive cells and synergy was not observed when both antibodies were used in combination. IgG1 was slightly more effective than IgG3. This animal model is a suitable alternative for conducting in vivo experiments in human beings, especially at the preclinical study phase of monoclonal anti-D antibodies.

Animals↗
PubMed1993

The R-C-E-F blood group system of chimpanzees: serology and genetics.

Six chimpanzee alloimmune antibodies define 20 phenotypes of the R-C-E-F blood group system, the counterpart of the human Rh system. Of the several specificities of this system, the Rc constitutes the crucial link with human Rh since the reactions of some chimpanzee alloimmune anti-Rc sera with human red cells parallel those obtained with human anti-Rho reagents. Reciprocally, properly absorbed human anti-Rho sera detect Rc specificity on chimpanzee red cells. Tests with large panels of human monoclonal anti-D antibodies confirm the notion of shared epitopes between human alloantigen Rho(D) and chimpanzee alloantigen Rc.

Alleles↗
PubMed1993

Quantitative study of chimpanzee and gorilla counterparts of the human D antigen.

The reactivities of three human anti-D monoclonal antibodies (mAbs) with human, chimpanzee, and gorilla red blood cells (RBCs) were compared by quantitative radioimmunology and indirect immunofluorescence methods. The number of antigenic sites varies widely in gorillas (from 48,000-283,000), while in chimpanzees this number is very close to that observed in human R1R2 RBCs. The affinity of the anti-D antibodies was slightly lower with ape RBCs than with D-positive human RBCs. In chimpanzee, the D-like epitopes recognition is enhanced by papain while the gorilla D-like epitopes are destroyed by enzyme treatment.

Animals↗
PubMed1993

Haplotypes of the human immunoglobulin lambda IGLV7S1 and IGLV1S1 genes defined by restriction-site polymorphism and insertion/deletion of a 6-kb DNA fragment.

Haplotypes were defined in the human immunoglobulin lambda locus by using three probes--V lambda VII, V lambda A, and V lambda I--hybridized to BamHI, KpnI, EcoRI, and HindIII digests. Four KpnI alleles were described. Two of them, 13 kb and 16 kb, detected with both the V lambda VII and V lambda A probes, were correlated with 4.6-kb and 10.5-kb KpnI fragments, respectively, which hybridize to the V lambda I probe. The two others (17 kb and 24 kb) were detected with the three probes V lambda VII, V lambda A, and V lambda I. Moreover, we show that two of those haplotypes may reflect an insertion of 6 kb between V lambda A and V lambda 1S1. Familial studies were performed to demonstrate the Mendelian inheritance. Our results demonstrate the absence of association between the C lambda alleles and V lambda haplotypes.

Antibody Diversity↗
PubMed1993

Relationship between chimpanzee Rh-like genes and the R-C-E-F blood group system.

The antigenic closeness between the chimpanzee alloantigen Rc of the R-C-E-F system, and the human alloantigen Rho(D) suggests a phyloge-connection between their genes. To confirm at the molecular level the common origin of these genes, genomic DNA from 16 unrelated chimpanzees of various R-C-E-F phenotypes were digested by three restriction enzymes and analyzed by Southern blot using a human Rh cDNA probe and three exon-specific probes. Restrictions profiles displayed reach polymorphism. Correlations between some bands and certain R-C-E-F phenotypes demonstrate that the human Rh cDNA probe defines in chimpanzee genomic DNA some genes of the R-C-E-F system.

Animals↗
PubMed1993

Immunoglobulin Gm allotypes in apes: comparison with man.

Serum samples from 245 apes (184 Pan troglodytes, five Pan paniscus, 28 Gorilla gorilla, 23 Pongo pygmaeus abelei, and five Pongo pygmaeus pygmaeus) were tested for G1m (1,2,3,17), G2m (23), and G3m (5,6,10,11,13,14,15,16,21,24,28) immunoglobulin allotypes by the classical method of inhibition of hemagglutination. Some phenotypes are species specific while a few are shared by man and African apes.

Animals↗
PubMed1993

Application of maximum likelihood statistics for the population and family studies of inheritance of the chimpanzee R-C-E-F and V-A-B-D blood groups.

Maximum likelihood statistics were applied to the analysis of serological data to confirm the originally proposed genetic models of the chimpanzee R-C-E-F and V-A-B-D systems. Five hundred ninety-nine chimpanzees, including 81 parents of 114 offspring, were tested for R-C-E-F, and 60 parents of 80 offspring were tested for V-A-B-D blood groups. An estimation-maximization procedure was used to obtain maximum likelihood estimates and support intervals of the haplotype frequencies. For each haplotype, the null hypothesis of nonexistence was evaluated. The frequencies obtained by this method do not differ significantly from those calculated by the square root formula, but put these estimates on a statistically more rigorous footing.

Animals↗
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↗