Induction of anti-arsonate CRI positive antibodies in BALB/c mice.
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Biomedical subjects
Publications and source records attributed to J Urbain.
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The ratio between inducer and cytotoxic/suppressor subset T-cells was studied in 11 cystic fibrosis patients and 11 non-cystic fibrosis controls. No statistically significant difference was found between the two groups. It is suggested that the major immune deficiency in some patients suffering from cystic fibrosis is a state of tolerance to the same bacterial antigens such as Pseudomonas aeruginosa. Inhibitory factors are present in the serum of the most affected patients.
Short homologies are often found when genetically unrelated proteins are compared but it is not known whether the rate at which they occur is or not above randomness. Comparing 190 pairs of unrelated proteins enable us to show that the frequency at which pairs of unrelated proteins share little spans of amino acids is compatible with chance. However, it appears that those short homologies are mainly located within protein subregions of identical secondary structure: the frequency at which pairs of unrelated proteins exhibit related spans of amino acids inside subregions of identical secondary structure is far above randomness. Those data suggest that the sharing of related spans of amino acids by genetically unrelated proteins could result from structural constraints imposed by the alpha or beta secondary structures.
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Hybridomas secreting antibodies against human urokinase have been produced by the cell-fusion technique (Köhler & Milstein, 1976). They belong to the IgG1 and IgG2 classes. Fixation and inhibition of the binding of 125 I-labelled urokinase, in radioimmunoassay, show that two of the monoclonal antibodies exhibit a high titer in ascitic fluids, a good sensitivity, and no cross reaction with other enzymes showing partial sequence homology with urokinase. Moreover, one of the monoclonal antibodies is able to inhibit the enzymatic activity of urokinase using a chromogenic substrate.
Suppressor T cells have been shown to be much more radiosensitive than other lymphoïd cells, and we have tried to reduce tumor growth by low-dose irradiation. Syngeneic DBA/2 mice received whole-body irradiation (150 rads; 1 rad = 0.01 J/kg) 6 days after P815 tumor inoculation. Tumor growth is significantly reduced in mildly irradiated mice. We also attempted to reduce syngeneic tumor growth by raising immunity against suppressor T cells in two different systems. DBA/2 mice were immunized against splenic T cells collected after disappearance of cytotoxicity and then injected with P815 tumor cells. These mice develop a very high primary cytotoxicity against P815 cells. C57BL/6 mice were immunized against blastic suppressor T cells, before injection of T2 tumor cells. Some of these mice reject the tumor and other develop smaller tumors than control mice. These results could be explained by the induction of antiidiotypic activity directed against the immunological receptors of suppressor T lymphocytes, because immunization with blastic suppressor T cells from mice bearing the T2 tumor does not modify the growth of another tumor, T10.
Specific idiotypie can be induced in randomly chosen rabbits by preimmunization with anti-idiotypic antibodies (Ab2). Rabbits that synthesize anti-anti-idiotypic antibodies (Ab3) when injected with antigen produce antibodies that display idiotypic specificities that are also found on the starting idiotype. When female rabbits actively producing Ab3 are crossed with naive males, a significant proportion of the offsprings (approximately 40%) produce antibodies that were idiotypically cross-reactive with the starting idiotype, as compared to 3% of the controls. This conclusion was obtained using 5 female rabbits and their 32 surviving offspring. Maternal idiotypes have therefore strong immunoregulatory properties and influence the emergence of the available idiotypic repertoire.
A total of 51 polypeptides of known amino acid sequence and secondary structure have been screened for the presence of symmetrical arrangements of amino acids. Similarity between amino acids was derived by using a genetic test (minimum mutation distance) or a structural test (relative frequencies of amino acids substitutions in families of related proteins). It is shown that the frequency of proteins displaying symmetrical arrangements of amino acids is slightly higher than predicted by chance. In contrast, when the analysis is restricted to protein subregions displaying identical types of secondary structure, the frequency of proteins in which the alpha and beta subregions exhibit symmetrical arrangements of amino acids is significantly higher than predicted by chance. On the other hand, it is observed that more discriminatory results are always obtained when the structural test is used as a criterion for amino acid similarity. These data suggest that symmetrical arrangements of amino acids could result from structural constraints imposed either by the alpha or beta secondary structures. It is postulated that the regular alternation in hydrophobicity which is generally observed in the amino acid sub-sequences displaying alpha or beta secondary structures may be responsible for the occurrence of symmetrical arrangements of amino acids.
Anti-idiotypic antibodies (Ab2) were raised in allotype-matched rabbits against anti-carbohydrate or anti-tobacco mosaic virus antibodies (Ab1). Several Ab2 were purified and injected into a third series of rabbits III which synthesized antiantiidiotypic antibodies (Ab3). Antigen was then given for the first time in those rabbits who had synthesized Ab3. The specific antibody synthesized in rabbits III was called Ab1'. Anti-idiotypic antibodies were raised against purified Ab3 antibodies (Ab4). In most cases, Ab1' antibodies are sharing idiotypic specificities with Ab1. Ab3 did not react with antigen but shared idiotopes with Ab1 and Ab1' because Ab4 antibodies, which are anti-idiotypes to Ab3 do recognize specifically Ab1 and Ab1' antibodies belonging to the same chain of immunization. It seems therefore that Ab3 looks idiotypically like Ab1 and Ab4 displays the same behaviour as Ab2. A general view of the functioning of the immune system is presented.
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During an immune response, the increase in binding affinity of antibodies is followed by a fall. Lymphocytes bearing autoanti-idiotypic receptors were detected during a normal immune response. The kinetics of appearance and disappearance of such lymphocytes led us to propose a network model to explain the changes occurring in antibody properties during an immune response.
Cattle and sheep infected by Bovine Leukemia Virus (BLV) harbor complement-dependent cytotoxic IgG1 antibodies. These antibodies lyse BLV producing cells but are inactive against noncultured tumorous lymphocytes of animals with persistent lymphocytosis. The target structure in the cell membrane contains antigenic determinants of BLV gp 60. The level of cytotoxic activity increases with progression of the disease towards the tumor phase. Sheep vaccinated with inactivated BLV have no cytotoxic activity in the serum but seem to resist infectious BLV challenge. Such cytotoxic activities do not protect the host against tumor growth but strongly control viremia and thus limit BLV spread within bovine and ovine populations.
The LOU/C/Wsl rat inbred strain presents a high incidence of spontaneous malignant ileocecal immunocytomas or monoclonal immunoglobulin-secreting tumors. Some tumors have been transplanted in histocompatible animals over years without any change in their secretion products. Among approximately 600 different monoclonal proteins we have studied so far, we recognized six showing properties different from those of rat IgM, IgA, IgE, or IgG classes, and characteristic of the IgD class.
Anticarbohydrate antibodies (Ab1) were isolated from a rabbit hyperimmunized with Micrococcus lysodeikticus and injected into allotype-matched rabbits in order to obtain specific anti-iodiotypic antibodies (Ab2). Ab2 was isolated by means of a Sepharose column coupled to the anticarbohydrate antibodies and was injected into two allotype-matched rabbits. These latter rabbits produced specific anti-anti-idiotypic antibodies (Ab3) probably sharing idiotypic specificities with Ab1. However, these Ab3 did not react with the antigenic carbohydrate moiety of bacteria. The two rabbits that had produced Ab3 were then immunized with M. lysodeikticus and synthesized anticarbohydrate antibodies (Ab1') bearing idiotypic specificities similar to those of Ab1. The immune repertoire which is effectively expressed in one individual depends not only on the antigenic stimulation but also on the previous idiotypic history of the individual. These data support the concept that the immune system is a functional idiotypic network.
We present a statistical method for detection of palindromes in mRNA or DNA, starting from the protein sequence. Analysis of immunoglobulin genes by this method demonstrates that palindromic sequences are not randomly distributed. They are located at each side of the hypervariable regions in the variable (V) genes, whereas no such regular design is observed in the constant (C) genes. In addition, palindromic sequences overlap the V-C junction in all immunoglobulin classes and significant palindromes are present near residue 216 of the heavy chain, which is the end of deletions in many heavy chain diseases. The relevance of these palindromes to gene translocation and generation of diversity in antibodies is discussed.
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Taking advantage of recent findings about membrane fluidity, we have studied and compared the biosynthetic capacities of fetal or neonatal mouse B (bone-marrow derived) lymphocytes (until 10 days after birth) and adult B lymphocytes. Although both early and adult lymphocytes can synthesize surface immunoglobulins, they have a different physiological behavior after interaction with a ligand (anti-immunoglobulin sera or antigen), either in vivo or in vitro. Fetal and neonatal lymphocytes bearing surface immunoglobulins do not reexpress their membrane receptors after capping and endocytosis promoted by anti-immunoglobulin sera. On the other hand, adult lymphocytes resynthesize completely their receptors after the same treatment. Furthermore, intrafetal injections of hemocyanin in pregnant mice lead to a striking decrease in the number of hemocyanin-binding cells. It seems plausible that this non-reexpression of surface immunoglobulins could be the first step in tolerance establishment.