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Biomedical subjects

J Urbain

Publications and source records attributed to J Urbain.

At least 109 records · Page 6Linked to original sources
PubMed1985

Towards a logical analysis of the immune response.

We present a new way to conceive, formalize and analyse models of the immune network. The models proposed are minimal ones, based essentially on the well-established negative feedback loop between helper and suppressor T cells. The occurrence of T-T interactions in both helper and suppressor circuits. These T-T interactions are represented here by autocatalytic feedback loops on TH and TS. The fact that immature B cells are sensitive to negative signaling, as was originally suggested by Lederberg (1959). There is a functional inactivation of immature B cells encountering antigen or anti-idiotypic antibody. This prevents further differentiation to a stage where the B cells become fully responsive. We describe the role of a logical method in the generation and analysis of the models, and the complementarity between this logical method and the more classical description by continuous differential equations. Logical analysis and numerical simulations of the differential equations show that the emerging model accounts for, the occurrence of multiple steady states (a virgin state, a memory state and a non-responsive state) in the absence of antigen, the kinetics of primary and secondary responses, high dose paralysis, low dose of paralysis. Its fit with real situations is surprisingly good for a model of this simplicity. Nevertheless, we give it as an example of what can now be done in the field rather than as a stable model.

Antibody Formation↗
PubMed1985

Enhancement of antibody response by mouse dendritic cells pulsed with tobacco mosaic virus or with rabbit antiidiotypic antibodies raised against a private rabbit idiotype.

The role of splenic lymphoid dendritic cells (DC) and macrophages (M phi) from mice in induction of immune responses in vivo has been investigated. Varying numbers of purified DC and M phi pulsed in vitro with tobacco mosaic virus (TMV) or with rabbit antiidiotypic antibodies (Ab2) directed against a private rabbit anti-TMV idiotype were injected back into syngeneic mice. In both systems, DC appeared to strongly enhance the primary and secondary responses to the virus. Optimal responses were obtained with 5 X 10(4) purified DC carrying TMV or rabbit Ab2. In contrast, M phi were less efficient by a factor of at least 100. These results show the potency of lymphoid DC as inducing cells in T-dependent antibody responses in vivo.

Animals↗
PubMed1985

Monoclonal antibodies against plasma protease inhibitors: production and characterization of 15 monoclonal antibodies against human antithrombin III. Relation between antigenic determinants and functional sites of antithrombin III.

Fifteen hybridomas secreting monoclonal antibodies against human antithrombin III, originating from two mouse strains, have been produced by the cell fusion technique. Eight monoclonal antibodies belong to the class IgG1, five to the class IgG2a, and two to the class IgG2b. All light chains belong to the kappa group. No cross-reaction of the monoclonal antibodies have been observed with a crude preparation of albumin nor with alpha 1-antitrypsin and alpha 2-antiplasmin. Five of these monoclonal antibodies exhibit a relatively high avidity for antithrombin III. Inhibition experiments showed that the 15 monoclonal antibodies define seven more or less independent antigenic regions on the antithrombin III molecule. Examination of the effects of these antibodies on the inhibitory capacity of antithrombin III toward thrombin activity, either in the presence or in the absence of heparin, showed that several monoclonal antibodies inhibit the antithrombin III activity and allowed to relate some of the antigenic determinants to functional sites on the antithrombin III molecule.

Animals↗
PubMed1985

Idiotypic analysis of polyclonal and monoclonal anti-p-azophenylarsonate antibodies of BALB/c mice expressing the major cross-reactive idiotype of the A/J strain.

The idiotypic cascade allows the induction of silent idiotypes, and as such, the immune system can be reprogrammed towards predetermined goals. To understand the genetic origin of silent idiotypes, we have used a system in which detailed structural and genetic information is available. The major cross-reactive idiotype (CRIA) of A/J mice (positive strain) immunized with arsonate coupled to a carrier can be regularly induced in BALB/c mice (negative strain) by anti-idiotypic treatment with or without subsequent antigen immunization. By using a panel of monoclonal anti-idiotypic antibodies, we have found that the germline-encoded CRIA displays a mosaic of at least five idiotopes. Polyclonal and monoclonal anti-arsonate antibodies prepared from idiotypically manipulated BALB/c mice have been studied. Four germline idiotopes are shared between the CRIA of the A/J strain and the CRIA-like idiotype induced in BALB/c mice. Furthermore, CRIA-like antibodies can appear "spontaneously" in some BALB/c mice immunized with antigen only. The data suggest that anti-idiotypic treatment in BALB/c mice selects a preexisting subset of antibodies. From the serological analysis, it is predicted that CRIA molecules from A/J and CRIA-like molecules from BALB/c employ different VH subgroups but share some components of the hypervariable regions. These predictions are tested in a forthcoming paper that describes the amino acid sequences of BALB/c monoclonal antibodies displaying the major cross-reactive idiotype of the A/J strain.

Amino Acid Sequence↗
PubMed1984

Induction of anti-tobacco mosaic virus antibodies in mice by rabbit antiidiotypic antibodies.

Conventional rabbit antiidiotypic antibodies were raised against a private rabbit anti-tobacco mosaic virus (TMV) idiotype. These rabbit antiidiotypic antibodies were covalently coupled to lipopolysaccharide and then injected into BALB/c mice. As compared with controls, these mice, which have never seen the antigen, synthesized anti-TMV antibodies that are strongly idiotypically cross-reactive with the starting rabbit idiotype. Monoclonal anti-TMV antibodies were prepared from these mice. Furthermore, xenogeneic or syngeneic antiidiotypic antibodies, raised against these monoclonal anti-TMV antibodies, recognized specifically the rabbit idiotype. Rabbit antiidiotypic antibodies alone can induce the same effects, but the concentration of anti-TMV antibodies is lower.

Animals↗
PubMed1984

Complete amino acid sequence of heavy chain variable regions derived from two monoclonal anti-p-azophenylarsonate antibodies of BALB/c mice expressing the major cross-reactive idiotype of the A/J strain.

The primary structure of A/J anti-p-azophenylarsonate (anti-Ars) antibodies expressing the major A-strain cross-reactive idiotype (CRIA) has provided important insights into issues of antibody diversity and the molecular basis of idiotypy in this important model system. Until recently, this idiotype was thought to be rarely, if ever, expressed in BALB/c mice. Indeed, it has been reported that BALB/c mice lack the heavy chain variable segment (VH) gene that is utilized by the entire family of anti-Ars antibodies expressing the A/J CRI. Recently, however, it has been possible to elicit CRIA+, Ars binding antibodies in the BALB/c strain by immunizing first with anti-CRI and then with antigen. Such BALB/c, CRIA+ anti-Ars antibodies can be induced occasionally with antigen alone. VH region amino acid sequences are described for two CRIA+ hybridoma products derived from BALB/c mice. While remarkably similar to each other, their VH segments (1-98) differ from the VH segments of A/J CRIA+, anti-Ars antibodies in over 40 positions. Rather than the usual JH2 gene segment used by most A/J CRIA+ anti-Ars antibodies, one BALB/c CRIA+ hybridoma utilizes a JH1 gene segment, while the other uses a JH4. However, the D segments of both of the BALB/c antibodies are remarkably homologous to the D segments of several A/J CRIA+ antibodies sequenced previously, as are the amino terminal amino acid sequences of their light chains. These data imply that BALB/c mice express the A/J CRIA by producing antibodies with very similar, if not identical, light chain and heavy chain D segments, but in the context of different VH and JH gene segments than their A/J counterparts. The results document that molecules that share serologic specificities can have vastly different primary structures.

Amino Acid Sequence↗
PubMed1984

Idiotypic analysis of potential and available repertoires in the arsonate system.

We have shown that, by suitable idiotypic manipulation, BALB/c mice can express the major cross-reactive idiotype (CRI) of A/J mice in response to azophenylarsonate (Ars). In order to know if the CRIA idiotype is present in the potential repertoire of BALB/c before any intentional selection, we used polyclonal activation in vitro and limiting dilution analysis. The readout was done with two monoclonal anti-CRIA antibodies that recognize distinct idiotopes on a CRIA+ A/J germline-encoded monoclonal antibody. We studied the frequency of CRIA+ lipopolysaccharide (LPS)-reactive cells in the spleens of nonimmune and immune A/J mice and in the spleens of naive and manipulated (i.e., producing CRIA+ antibodies) BALB/c mice. A/J and BALB/c naive individuals presented very high frequencies of Ars-specific B cells while the frequency of CRIA+ B cells was only a minor subset (0.5%) of the total Ars-specific subset in the two strains. When A/J mice were immunized with Ars-keyhole limpet hemocyanin, a clear preferential expansion of the CRIA+ minor subset of A/J mice was observed (100x). No such enhancement was observed in BALB/c mice similarly treated. Manipulated BALB/c mice presented a higher frequency of CRIA+ anti-Ars B cells than naive or antigen-immunized BALB/c individuals.

Animals↗
PubMed1984

Alpha secondary structures generate weak but recurrent periodicity in proteins.

Weak but recurrent periodic patterns characterize numerous actual proteins: the rate at which similarity occurs between residues i and i + 4 or i + 7 or i + 11 is very often slightly higher than predicted by chance. That result could indicate that numerous actual proteins derive from ancestral clearcut periodic sequences. Nevertheless, it is shown that this recurrent periodic pattern occurs much more significantly when analyses are restricted to the alpha-helical portions of proteins while it never occurs when beta-stranded subsequences are taken into account. This preferential location of periodicity inside protein subregions corresponding to alpha helices suggests that the recurrent pattern of weak periodicity could result from an ubiquitous physical property of alpha helices. The regular alternation of hydrophobicity, which is most often displayed by alpha helices, could then be the origin of weak periodicity.

Amino Acid Sequence↗
PubMed1984

Anti-immunoglobulin antibodies IV. Cross-reaction of anti-idiotypic antibodies specific for rabbit and murine anti-a1 allotype antibodies with Fc fragment of human immunoglobulins.

Anti-idiotype (Id) antibodies against anti-a1 rabbit allotype antibodies were produced in rabbits and mice by immunization with polyclonal rabbit anti-a1 allotype or with a monoclonal murine anti-a1 allotype antibody, respectively. These antibodies recognize an interspecies cross-reactive idiotope on anti-a1 allotype antibodies. However, these anti-Id antibodies also react with various subclasses of human IgG. In multiple systems, it was shown that these anti-Id antibodies interact with the Fc fragment of human IgG and, therefore, exhibit a rheumatoid factor-like activity. These results support the hypothesis that gamma-globulin may not be the only stimulus to clones producing rheumatoid factors and that perhaps other antibodies, especially anti-Id antibodies, also bind gamma-globulin secondarily.

Animals↗
PubMed1984

Monoclonal antibodies against plasma protease inhibitors: II. Production and characterization of 25 monoclonal antibodies against human alpha 1-antitrypsin. Correlation between antigenic structure and functional sites.

Twenty-five hybridomas secreting monoclonal antibodies against human alpha 1-antitrypsin have been produced by the cell-fusion technique (Köhler and Milstein, 1976). All antibodies are specific for alpha 1-antitrypsin and carry gamma 1 heavy chains and kappa light chains. Inhibition experiments showed that these monoclonal antibodies define three independent antigenic regions on the alpha 1-antitrypsin molecule; one of these domains appears to be involved in the interaction between alpha 1-antitrypsin and trypsin. In addition, one monoclonal antibody, AATY39, was used to develop an enzyme-linked immunosorbent assay capable of detecting low levels of alpha 1-antitrypsin in the range of 1 to 2 ng/ml.

Animals↗
PubMed1984

Monoclonal antibodies against plasma protease inhibitors: I. Production and characterization of 23 monoclonal antibodies against human alpha 2-antiplasmin.

23 hybridomas secreting monoclonal antibodies against human alpha 2-antiplasmin, the fast-acting inhibitor of plasmin present in plasma, have been produced by the cell-fusion technique. Isotyping of the monoclonal antibodies has revealed that 14 monoclonal antibodies belong to the class IgG1, 6 to the class IgG2a, and 3 to the class IgG2b. All light chains belong to the kappa group. The specificity and relative avidity of these monoclonals have been determined using an indirect enzyme-linked immunosorbent assay. 13 monoclonals exhibit a relatively high avidity for alpha 2-antiplasmin, 5 are of intermediate avidity, and 5 of low avidity. The epitope specificity of these 23 monoclonal antibodies, originating from a single mouse, have been examined in inhibition experiments. A group of 10 monoclonal antibodies exhibit a very similar inhibition pattern. Partial inhibition effects displayed by 10 other antibodies define partially overlapping antigenic regions. The binding of these antibodies seems to produce a conformational change in the alpha 2-antiplasmin molecule, reducing the binding of two other antibodies. The last antibody defines an independent epitope.

Animals↗
PubMed1984

Idiotypic manipulations: hierarchy in idiotype expression in rabbits immunized against Micrococcus luteus.

Idiotypic cross-reactions were analyzed among three series of anti-peptidoglycan antibodies of the Micrococcus luteus system. The reference idiotype Ab1 was an antibody fraction isolated from an isoelectric focusing preparative column. Cross-reactive idiotypes, Ab1', were induced through the immunization chain (Ab1-Ab2-Ab3). Idiotypic antibodies of Ab1-F1 type were obtained from offspring of female rabbits, actively producing Ab3 during pregnancy. Finally, Ab1 CRI were cross-reactive idiotypes with Ab1 found in a random population of rabbits immunized with M. luteus. Three idiotopes could be characterized within Ab1 antibody. Ab1' usually expressed two of these idiotopes, but never the third specificity which is "private" to Ab1. Ab1-F1 shared one or two idiotopes with Ab1 and Ab1' antibodies. Only one common idiotope appeared to be present on Ab1 CRI. Finally, this idiotope, IdX, could be detected by radioimmunoassay in 20% of rabbits immunized with micrococcal vaccine. It appears that a recurrent idiotype of anti-peptidoglycan antibodies can be preferentially amplified through idiotypic manipulations. On the other side, cascade immunizations lead to the expression on Ab1' and on some Ab1-F1 of a second idiotypic specificity, shared with Ab1. This hierarchy of idiotype expression may well be important in the regulation of antibody synthesis through idiotypes.

Animals↗
PubMed1983

Solid-phase enzyme immunoassay of urokinase using monoclonal antibodies.

Using two monoclonal antibodies directed against urokinase, we have developed a micro enzyme-linked immunosorbant assay (ELISA) to detect and measure urokinase in biological fluids. The system presents the following characteristics: simple and rapid procedure, reproducibility, sensitivity (urokinase levels down to 1 ng/ml) and evaluation of the enzyme in biological fluids such as urine, pleural effusions, and ascitic fluids without preliminary purification.

Antibodies, Monoclonal↗
PubMed1983

Idiotypic studies of monoclonal anti-tobacco mosaic virus antibodies from one mouse.

Monoclonal antibodies have been prepared from one BALB/c mouse immunized with tobacco mosaic virus. The monoclonal antibodies are distributed into three subgroups recognizing different epitopes on tobacco mosaic virus subunits. The idiotypic specificities of these monoclonal antibodies have been studied using syngeneic antiidiotypic sera. A sharing of idiotypic specificities has been observed between members of each subset. These idiotypes are not recurrent in BALB/c mice immunized with tobacco mosaic virus.

Animals↗
PubMed1983

Idiotypic manipulation in mice: BALB/c mice can express the crossreactive idiotype of A/J mice.

The response of A/J mice to arsonate-coupled keyhole limpet hemocyanin is characterized by a crossreactive idiotype (CRIA). CRIA+ antibodies are restricted to the Igh-Ic haplotype and are never expressed in BALB/c mice after immunization with antigen. Studies at the DNA level suggest that the gene encoding the CRIA heavy chain in A/J mice is probably absent in the genome of BALB/c mice. Despite this, using the immunization cascade tool, we have been able to induce the expression of CRIA+ antibodies in BALB/c mice. These studies led to an apparent paradox, whose understanding will provide new insights into the regulatory mechanisms of the immune system. We suggest that clones secreting CRIA-like Igs in BALB/c mice are "somatic variants" that could arise from gene conversion events.

Animals↗