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H Zaghouani

Publications and source records attributed to H Zaghouani.

49 records · Page 3Linked to original sources
PubMed1990

Autoantibodies, LY-1, and immunoglobulin V gene expression in hybridomas obtained from young and from old New Zealand black mice.

We obtained a large number of hybridomas from 1-month-old and 16-month-old New Zealand black mice to study the fine specificities of the autoantibodies produced, the expression of Ly-1, and the expression of the immunoglobulin V gene families in this autoimmune strain. Analysis of the autoantibody specificities yielded 2 major classifications: those specific for a single autoantigen and those that exhibited multispecific binding. Among the multispecific antibodies, 2 categories were found: an antigen-inhibitable group and an antigen-noninhibitable group. A large proportion of VHJ558 and VH7183 gene families was observed in hybridomas obtained from 1-month-old mice, and in hybridomas obtained from 16-month-old mice, there was a large proportion of VHJ558 and VH36-60 gene families. Among the autoantibody kappa chains secreted by the hybridomas, there was a higher frequency of the V kappa 1, V kappa 8, and V kappa 9 gene families. Autoantibodies were produced by both the Ly-1+ and the Ly-1- B cell subsets.

Age Factors↗
PubMed1990

Ly1 and V-gene expression among hybridomas secreting natural autoantibody.

This report presents evidence that multispecific natural autoantibodies (NAAb) arise from both Ly-1+ and Ly-1- B lymphocyte subsets based upon detection of mRNA transcript of Ly1 gene by Northern blotting among hybridomas from several mouse strains. Newborn Xid mice also possess B cells transcribing the Ly-1 gene that secrete multispecific NAAbs. Different VH and VK gene families were expressed at random in both Ly-1+ and Ly-1- hybridoma clones secreting NAAbs. Certain VK gene families VK1, -8, -9, -10 and -19, were preferentially used by NAAbs. No particular VH:VK pairings were observed among NAAbs multispecifically reactive with DNA and cytoskeleton proteins. The NAAbs reactive with BrMRBC exhibited predominant pairing between VH11:VK9 gene families, although, for the first time, we noted the participation of VK1, -10 and -19 gene families in encoding this autoantibody specificity.

Animals↗
PubMed1990

The LY-1 gene expression in murine hybridomas producing autoantibodies.

Studies presented here demonstrate the expression of the Ly-1 gene and the detection of the Ly-1 cytodifferentiation antigen in murine hybridomas producing autoantibodies. We examined the transcription of the Ly-1 gene in thymocytes and 140 hybridomas producing autoantibodies of various specificities which were obtained from normal and autoimmune disease prone mouse strains. As previously demonstrated thymocytes stain brightly for Ly-1 by immunofluorescence and express Ly-1 transcripts. In our panel of hybridomas producing autoantibodies Ly-1 transcripts were detected in 31 (45%) out of 69 NZB hybridomas and 7 (88%) out of 8 viable motheaten hybridomas. S1 nuclease protection experiments showed that Ly-1 transcripts detected in thymocytes and B cells are the product of the same gene. The B cell transcripts are functional since immunofluorescence and Western data presented here detected the Ly-1 protein in hybridomas cells which were found to transcribe the Ly-1 gene. Interestingly a polymorphic transcription of the Ly-1 gene was observed in B cells and B cell hybridomas as compared to thymocytes. Our results obtained in the hybridoma system firmly establish a major contribution of the Ly-1 B cell subset to the production of DNA specific autoantibodies and a smaller contribution to the production of rheumatoid factors and "natural", multispecific autoantibodies.

Animals↗
PubMed1989

Molecular basis for expression of the A48 regulatory idiotope on antibodies encoded by immunoglobulin variable-region genes from various families.

The idiotype defined by the levan-specific BALB/c myeloma protein ABPC48 (A48) has previously been encountered only in antibodies the variable regions of which derive from the VHX24 and V kappa 10 gene families. We have demonstrated expression of the idiotope recognized by the monoclonal anti-A48 idiotype antibody IDA10 on five monoclonal antibodies from different mouse strains, with different specificities including foreign and self antigens and deriving their variable regions from families other than VHX24 and V kappa 10. We analyzed variable region protein structure (deduced from nucleotide sequences) and hydrophilicity profiles of idiotype+ and idiotype- antibodies. We identified four surface-exposed areas (one in the heavy chain and three in the light chain) that may contribute to expression of the idiotope defined by antibody IDA10.

Animals↗
PubMed1989

Oligomeric structure of gp41, the transmembrane protein of human immunodeficiency virus type 1.

We characterized the structural forms of the human immunodeficiency virus env-encoded proteins with a panel of monoclonal and polyclonal antibodies. Western blot (immunoblot) assays with antibodies specific for gp41 invariably recognized a major component of 160 kilodaltons and a less intense component of 120 kilodaltons in viral lysates. We demonstrated that these species are noncovalently associated tetramers and trimers of gp41 which represent the native form of this protein in virions. These complexes were stable when boiled in the presence of low concentrations of sodium dodecyl sulfate but were dissociated to gp41 monomers at high sodium dodecyl sulfate concentrations. Moreover, two human monoclonal antibodies preferentially recognized the oligomeric complexes over monomeric gp41 in Western blots, indicating the presence of epitopes recognized by the human immune system on the gp41 multimers which are not efficiently expressed by the dissociated monomers. The demonstration of the existence of multimeric env complexes and the enhanced and altered antigenicity of such multimers may be relevant to the design of subunit and recombinant human immunodeficiency virus env vaccines.

Antibodies, Monoclonal↗
PubMed1988

A new strain-specific cross-reactive idiotope with possible regulatory function expressed on BALB/c anti-alpha (1-3) dextran antibodies.

We obtained a mAb, B5, defining a major crossreactive Id, the B5 Id, having an in vivo regulatory function. BALB/c mice immunized against the bacterial dextran Ag B1355S produce lambda 1-bearing anti-alpha (1-3) glucosidic linkage of dextran B1355S (DEX) antibodies. Of these antibodies 30% expressed the B5 Id determinant. As was observed for the IdX-Id, B5 idiotope expression was also linked to the BALB/c H chain allotype. The antibody family expressing the B5 Id included IdX+ as well as IdX- defined monoclonal anti-alpha (1-3) DEX antibodies. Injection into BALB/c mice of mAb B5 conjugated to keyhole limpet hemocyanin led to enhancement of serum anti-alpha (1-3) DEX antibody synthesis, and to a strong increase in B5+ Ig lacking dextran-binding activity. IdX+ serum Ig were also increased in these mice. Injection of this mAb into allotype congenic nonresponder C.B20 mice induced a significant serum lambda 1-bearing anti-alpha (1-3) dextran antibody response (5 to 50 micrograms/ml). However, in A/J nonresponder mice, a similar treatment induced only the dextran-nonbinding component, which reached high levels (approximately 7 mg/ml) in the sera of these mice. In the majority of these A/J mice, we detected a specific anti-(4-hydroxy-5-iodo-3-nitrophenyl)acetyl antibody response characterized by B5 Id-positive antibodies. This observation can be explained by an in vivo regulatory idiotope-mediated cross-regulation.

Adjuvants, Immunologic↗
PubMed1987

Regulation of the response to alpha(1-3) dextran: an anti-dextran associated idiotope of BALB/c mice is also expressed on A/J anti-NIP antibodies.

The functional properties of a mAb reactive to the B5 idiotope were analyzed in BALB/c, A/J and C.B20 mice. the B5 idiotope was specifically associated with the alpha(1-3) DEX response in a strain-specific manner in BALB/c mice (responder strain). It was serologically distinct from the previously described IdX idiotype and overlapped on part of the IdX+ and IdX- BALB/c anti-alpha(1-3) DEX response. While treatment of adult BALB/c mice with mAb B5 enhanced the serum anti-alpha(1-3) DEX antibody synthesis and induced de novo antibody synthesis in non-responder C.B20 mice, A/J non-responder mice remained unresponsive, despite elevated levels of serum B5+ dextran non-binding Ab3 immunoglobulins. However, in some of these A/J mice, we detected an enhancement of anti-NIP antibody synthesis. This anti-NIP antibody component was (1) specifically induced by mAb B5, (2) found in A/J, but not in BALB/c or C.B20 mice, and (3) specific towards the NIP hapten. These A/J anti-NIP antibodies bore either the lambda 1 or the kappa light chain and some of them also expressed the B5 idiotope. The B5 id thus appears as a typical id determinant shared by antibodies having different binding specificities, and it may have a role in the regulation of these responses.

Animals↗
PubMed1986

Monoclonal anti-alpha (1----3) dextran antibodies of Igha BALB/c and Ighb C.B20 mice display striking similarities.

Allotype Ighb congenic C.B20 mice when immunized with dextran B1355S are unable to produce anti-alpha (1----3) dextran antibodies that express the VH-associated cross-reactive IdX idiotype. This intrastrain-specific idiotype is normally associated only with the anti-dextran response of Igha mice of which BALB/c is a prototype strain. In this study we have obtained monoclonal hybridoma antibodies specific for the alpha (1----3) glucosidic linkage of dextran from C.B20 mice that were presensitized with rabbit anti-IdX antibodies. These antibodies display the light chain isotype distribution, the H chain amino terminal sequence, share VH-associated IdX idiotypic determinants, and finally the similar fine specificity for dextrans observed for anti-alpha (1----3) dextran antibodies of BALB/c mice.

Amino Acid Sequence↗
PubMed1986

Monoclonal antibodies against oncofetal mucin M1 antigens associated with precancerous colonic mucosae.

We obtained seven monoclonal antibodies (MAb) against a gastric mucin of an ALeb patient. By immunoperoxidase on normal gastric mucosae, two MAbs (3-3A and 2-25 LE) reacted exclusively with the A and Lewis-positive individuals, respectively; the five other MAbs (1-13 M1, 2-11 M1, 2-12 M1, 9-13 M1, and 58 M1) stained the mucus cells of surface gastric epithelium independently of ABO or Lewis status. They did not stain normal colonic mucosae, but did stain fetal and precancerous colonic mucosae. Using serial sections, each anti-M1 MAb stained the same goblet cells in fetal and precancerous colon. Extensive search of other normal tissues showed that M1 antigens were restricted to the epithelium embryologically derived from the foregut (gastric and bronchial epithelium) and from Müllerian ducts (mucus cells of endocervix and prostatic utriculus). Some differences in the reactivities of the various anti-M1 MAb were observed in subesophageal, subtracheal, and endocervical mucus cells, suggesting that each anti-M1 MAb characterized a different M1 epitope. A mixture of these five anti-M1 MAbs allowed the estimation of M1 mucus modification in the precancerous colonic mucosae with a sensitivity near to that obtained with polyclonal anti-M1 antibodies. Papain and mercaptoethanol treatments destroyed the M1 epitopes, at variance with the A- or Lewis-related antigens. Our results therefore suggest that the expression of M1 epitopes in precancerous colonic mucosae cannot be due exclusively to alterations in mucin glycosylation but may be related to the reexpression of antigens associated with native gastric mucin which is normally produced by the fetal colon during the sixth month of gestation.

Adolescent↗
PubMed1983

Induction of a cross-reactive idiotype dextran-positive antibody response in two IgH-Cb mouse strains treated with anti-J558 cross-reactive idiotype antibodies.

The effect of IdX-specific rabbit and allogeneic antiidiotype antibodies (Ab2) was investigated in vivo in Igh-Cb mouse strains with respect to the induction of a cross-reactive idiotype (IdX)-positive anti-alpha (1-3) Dextran (Dex) response. These C.B20 and C57Bl/6 mice have an allotype-linked incapacity to respond with IdX-positive anti-alpha (1-3) Dex antibodies upon conventional immunization with Dex B1355. 7 d after the rabbit Ab2 injections, IdX-positive Ig (Ab3) and IdX-positive anti-alpha (1-3) Dex antibodies (Ab1') were detected in the sera of each tested mouse. The affinity-purified Ab1' were idiotypically indistinguishable from reference BALB/c IdX-positive myeloma proteins and BALB/c anti-alpha (1-3) Dex antibodies (Ab1) in a competitive inhibition radioimmunoassay, while Ab3 Ig appeared idiotypically deficient and did not bind to Dex. The response to the alpha (1-6) linkage of Dex was not affected in these mice. A large fraction of the Ab1' and Ab3 responses of both mouse strains were of the IgG1 class. The Ab1' antibodies differed from BALB/c Ab1 by lower relative binding to five of eight tested Dex, and by expressing the Igh4b allotype determinants on the IgG1 antibodies. This study identifies the products of a VHDex gene that appears to be under regulatory control in the Ighb mice. Its association with the b haplotype suggests that this gene may differ structurally from the BALB/c VHDex gene.

Animals↗
PubMedDate not supplied

The significance of idiotype-anti-idiotype interactions in the activation of self-reactive clones.

Autoantibodies against a wide range of self antigens have been found in the serum of normal mice and healthy humans. It is now accepted that the production of self reactive clones is not an aberration and that the immune system does not purge itself of the previously called "horror" clones. Recently it has been shown that the majority of autoantibodies are polyspecific and able to react with both self and foreign antigens. Following these observations, it was speculated that the activation of self reactive clones may result from common shared epitopes between self and foreign (bacterial, viral and parasitic) antigens. In this report, we show on the one hand that autoantibodies specific for Sm antigen express an idiotype originally found on antibodies specific for bacterial levan. On the other hand, using an anti-idiotypic antibody bearing the internal image of the glutamic-tyrosine polymer, we succeed in inducing polyspecific antibodies reacting with GT and self antigens in both normal and autoimmune disease prone mice. These findings may reflect one side of the mechanism(s) behind the activation of self reactive clones. The significance of idiotype-anti-idiotype interactions in the activation of self reactive clones which may be responsible for autoimmune diseases is discussed.

Animals↗