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Jeanpol Frippiat - One of the best experts on this subject based on the ideXlab platform.
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The urodele amphibian Pleurodeles waltl has a diverse repertoire of Immunoglobulin Heavy Chains with polyreactive and species-specific features
Developmental and Comparative Immunology, 2015Co-Authors: Coralie Fonte, Arnaud Gruez, Stephanie Ghislin, Jeanpol FrippiatAbstract:Urodele amphibians are an interesting model because although they possess the cardinal elements of the vertebrate immune system, their immune response is apparently subdued. This phenomenon, sometimes regarded as a state of immunodeficiency, has been attributed by some authors to limited antibody diversity. We reinvestigated this issue in Pleurodeles waltl, a metamorphosing urodele, and noted that upsilon transcripts of its IgY repertoire were as diverse as alpha transcripts of the mammalian IgA repertoire. Mu transcripts encoding the IgM repertoire were less diverse, but could confer more plasticity. Both isotypes present potential polyreactive features that may confer urodele antibodies with the ability to bind to a variety of antigens. Finally, we observed additional cysteines in CDR1 and 2 of the IGHV5 and IGHV6 domains, some of which specific to urodeles, that could allow the establishment of a disulfide bond between these CDRs. Together, these data suggest that urodele antibody diversity is not as low as previously thought.
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effects of a long term spaceflight on Immunoglobulin Heavy Chains of the urodele amphibian pleurodeles waltl
Journal of Applied Physiology, 2005Co-Authors: Rachel Boxio, Christian Dournon, Jeanpol FrippiatAbstract:A variety of immune parameters are modified during and after a spaceflight. The effects of spaceflights on cellular immunity are well documented; however, little is known about the effects of these flights on humoral immunity. During the Genesis space experiment, two adult Pleurodeles waltl (urodele amphibian) stayed 5 mo onboard Mir and were subjected to oral immunization. Animals were killed 10 days after their return to earth. IgM and IgY Heavy-chain transcripts in their spleens were quantified by Northern blotting. The use of the different VH families (coding for antibody Heavy-chain variable domains) in IgM Heavy chain transcripts was also analyzed. Results were compared with those obtained with ground control animals and animals reared in classical conditions in our animal facilities. We observed that, 10 days after the return on earth, the level of IgM Heavy-chain transcription was normal but the level of IgY Heavy-chain transcription was at least three times higher than in control animals. We also observed that the use of the different VH families in IgM Heavy-chain transcripts was modified by the flight. These data suggest that the spaceflight affected the antibody response against the antigens contained in the food.
Alan G Marshall - One of the best experts on this subject based on the ideXlab platform.
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classification of plasma cell disorders by 21 tesla fourier transform ion cyclotron resonance top down and middle down ms ms analysis of monoclonal Immunoglobulin light Chains in human serum
Analytical Chemistry, 2019Co-Authors: Lissa C Anderson, David R Barnidge, David L Murray, Surendra Dasari, Angela Dispenzieri, Christopher L Hendrickson, Alan G MarshallAbstract:The current five-year survival rate for systemic AL amyloidosis or multiple myeloma is ∼51%, indicating the urgent need for better diagnosis methods and treatment plans. Here, we describe highly specific and sensitive top-down and middle-down MS/MS methods owning the advantages of fast sample preparation, ultrahigh mass accuracy, and extensive residue cleavages with 21 telsa FT-ICR MS/MS. Unlike genomic testing, which requires bone marrow aspiration and may fail to identify all monoclonal Immunoglobulins produced by the body, the present method requires only a blood draw. In addition, circulating monoclonal Immunoglobulins spanning the entire population are analyzed and reflect the selection of germline sequence by B cells. The monoclonal Immunoglobulin light chain FR2-CDR2-FR3 was sequenced by database-aided de novo MS/MS and 100% matched the gene sequencing result, except for two amino acids with isomeric counterparts, enabling accurate germline sequence classification. The monoclonal Immunoglobulin Heavy Chains were also classified into specific germline sequences based on the present method. This work represents the first application of top/middle-down MS/MS sequencing of endogenous human monoclonal Immunoglobulins with polyclonal Immunoglobulins background.
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Classification of Plasma Cell Disorders by 21 Tesla Fourier Transform Ion Cyclotron Resonance Top-Down and Middle-Down MS/MS Analysis of Monoclonal Immunoglobulin Light Chains in Human Serum
2019Co-Authors: Lissa C Anderson, David R Barnidge, David L Murray, Surendra Dasari, Angela Dispenzieri, Christopher L Hendrickson, Alan G MarshallAbstract:The current five-year survival rate for systemic AL amyloidosis or multiple myeloma is ∼51%, indicating the urgent need for better diagnosis methods and treatment plans. Here, we describe highly specific and sensitive top-down and middle-down MS/MS methods owning the advantages of fast sample preparation, ultrahigh mass accuracy, and extensive residue cleavages with 21 telsa FT–ICR MS/MS. Unlike genomic testing, which requires bone marrow aspiration and may fail to identify all monoclonal Immunoglobulins produced by the body, the present method requires only a blood draw. In addition, circulating monoclonal Immunoglobulins spanning the entire population are analyzed and reflect the selection of germline sequence by B cells. The monoclonal Immunoglobulin light chain FR2-CDR2-FR3 was sequenced by database-aided de novo MS/MS and 100% matched the gene sequencing result, except for two amino acids with isomeric counterparts, enabling accurate germline sequence classification. The monoclonal Immunoglobulin Heavy Chains were also classified into specific germline sequences based on the present method. This work represents the first application of top/middle-down MS/MS sequencing of endogenous human monoclonal Immunoglobulins with polyclonal Immunoglobulins background
J Jami - One of the best experts on this subject based on the ideXlab platform.
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pre b cell development in the absence of λ5 in transgenic mice expressing a Heavy chain disease protein
Current Biology, 1995Co-Authors: Daniel Corcos, O Dunda, D Bucchini, Cecile Butor, Jeanyves Cesbron, Patrick Lores, J JamiAbstract:Abstract Background: Heavy-chain diseases (HCDs) are human lymphoproliferative neoplasias that are characterized by the secretion of truncated Immunoglobulin Heavy Chains devoid of light Chains. We have previously proposed — by analogy to the process by which mutated growth factor receptors can be oncogenic — that because the genetic defects in HCDs result in the production of abnormal membrane-associated Heavy Chains lacking an antigen-binding domain, these abnormal B-cell antigen receptors might engage in ligand-independent signalling. Normal pre-B-cell development requires the presence of the pre-B-cell receptor, formed by the association of μ Heavy Chains with two polypeptides — so-called surrogate light Chains, V pre-B and λ5 — that are homologous to the variable and constant portions of Immunoglobulin light Chains, respectively. To assess whether amino-terminal truncation of membrane-associated Heavy Chains results in their constitutive activation, we have examined the ability of a HCD-associated μ protein to promote pre-B-cell development in transgenic mice. Results When the μ HCD transgene is introduced into SCID mice, CD43 − pre-B cells develop normally. To determine whether this pre-B-cell development requires surrogate light Chains, we backcrossed mice expressing full-length or truncated μ transgenes with λ5-deficient mice. Our results show that the truncated Heavy chain, but not the normal chain, is able to promote pre-B-cell development in the absence of λ5. We also show that truncated μ Chains spontaneously aggregate at the surface of bone marrow cells. Conclusion Expression of the truncated μ Heavy chain overrides a tightly controlled step of pre-B-cell development, which strongly suggests that a constitutive signal is delivered by the truncated μ chain disease protein. The self-aggregation of μ chain disease proteins might account for this constitutive activation. We conclude that amino-terminal truncation of Heavy Chains could play a role in the genesis of HCD neoplasia if it occurs at an appropriate stage of B-cell differentiation, namely in a mature B cell.
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allelic exclusion in transgenic mice expressing a Heavy chain disease like human μ protein
European Journal of Immunology, 1991Co-Authors: Daniel Corcos, Antonio Iglesias, O Dunda, D Bucchini, J JamiAbstract:Heavy chain diseases (HCD) are neoplastic proliferations of B cells which secrete truncated Immunoglobulin Heavy Chains without associated light Chains. These proteins are encoded by mutated genes which may also give rise to truncated membrane Immunoglobulins. The neoplastic cells proliferate in vivo although they cannot bind any antigen, due to deletions in the variable domain of their antigen receptors. The reason for the clonal proliferation of HCD cells and the biological effects of the truncated membrane-bound Chains are presently unknown. We wanted to determine whether the expression of HCD proteins would interfere with B cell development. To this end we made transgenic mice with a human mu gene, lacking the VDJ exon, that encodes a protein similar to that produced in two cases of HCD. Transgenic mice were also produced with a similar construct but encoding only the membrane-bound form of the truncated mu chain. Transgene encoded C mu proteins are expressed on the cell surface without associated light Chains and are responsible for allelic exclusion of murine Heavy Chains.
Lissa C Anderson - One of the best experts on this subject based on the ideXlab platform.
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classification of plasma cell disorders by 21 tesla fourier transform ion cyclotron resonance top down and middle down ms ms analysis of monoclonal Immunoglobulin light Chains in human serum
Analytical Chemistry, 2019Co-Authors: Lissa C Anderson, David R Barnidge, David L Murray, Surendra Dasari, Angela Dispenzieri, Christopher L Hendrickson, Alan G MarshallAbstract:The current five-year survival rate for systemic AL amyloidosis or multiple myeloma is ∼51%, indicating the urgent need for better diagnosis methods and treatment plans. Here, we describe highly specific and sensitive top-down and middle-down MS/MS methods owning the advantages of fast sample preparation, ultrahigh mass accuracy, and extensive residue cleavages with 21 telsa FT-ICR MS/MS. Unlike genomic testing, which requires bone marrow aspiration and may fail to identify all monoclonal Immunoglobulins produced by the body, the present method requires only a blood draw. In addition, circulating monoclonal Immunoglobulins spanning the entire population are analyzed and reflect the selection of germline sequence by B cells. The monoclonal Immunoglobulin light chain FR2-CDR2-FR3 was sequenced by database-aided de novo MS/MS and 100% matched the gene sequencing result, except for two amino acids with isomeric counterparts, enabling accurate germline sequence classification. The monoclonal Immunoglobulin Heavy Chains were also classified into specific germline sequences based on the present method. This work represents the first application of top/middle-down MS/MS sequencing of endogenous human monoclonal Immunoglobulins with polyclonal Immunoglobulins background.
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Classification of Plasma Cell Disorders by 21 Tesla Fourier Transform Ion Cyclotron Resonance Top-Down and Middle-Down MS/MS Analysis of Monoclonal Immunoglobulin Light Chains in Human Serum
2019Co-Authors: Lissa C Anderson, David R Barnidge, David L Murray, Surendra Dasari, Angela Dispenzieri, Christopher L Hendrickson, Alan G MarshallAbstract:The current five-year survival rate for systemic AL amyloidosis or multiple myeloma is ∼51%, indicating the urgent need for better diagnosis methods and treatment plans. Here, we describe highly specific and sensitive top-down and middle-down MS/MS methods owning the advantages of fast sample preparation, ultrahigh mass accuracy, and extensive residue cleavages with 21 telsa FT–ICR MS/MS. Unlike genomic testing, which requires bone marrow aspiration and may fail to identify all monoclonal Immunoglobulins produced by the body, the present method requires only a blood draw. In addition, circulating monoclonal Immunoglobulins spanning the entire population are analyzed and reflect the selection of germline sequence by B cells. The monoclonal Immunoglobulin light chain FR2-CDR2-FR3 was sequenced by database-aided de novo MS/MS and 100% matched the gene sequencing result, except for two amino acids with isomeric counterparts, enabling accurate germline sequence classification. The monoclonal Immunoglobulin Heavy Chains were also classified into specific germline sequences based on the present method. This work represents the first application of top/middle-down MS/MS sequencing of endogenous human monoclonal Immunoglobulins with polyclonal Immunoglobulins background
Masatoshi Nei - One of the best experts on this subject based on the ideXlab platform.
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Evolutionary dynamics of the Immunoglobulin Heavy chain variable region genes in vertebrates
Immunogenetics, 2008Co-Authors: Sabyasachi Das, Masafumi Nozawa, Jan Klein, Masatoshi NeiAbstract:Immunoglobulin Heavy Chains are polypeptides encoded by four genes: variable ( IGHV ), joining ( IGHJ ), diversity ( IGHD ), and constant ( IGHC ) region genes. The number of IGHV genes varies from species to species. To understand the evolution of the IGHV multigene family, we identified and analyzed the IGHV sequences from 16 vertebrate species. The results show that the numbers of functional and nonfunctional IGHV genes among different species are positively correlated. The number of IGHV genes is relatively stable in teleosts, but the intragenomic sequence variation is generally higher in teleosts than in tetrapods. The IGHV genes in tetrapods can be classified into three phylogenetic clans (I, II, and III). The clan III and/or II genes are relatively abundant, whereas clan I genes exist in small numbers or are absent in most species. The genomic organization of clan I, II, and III IGHV genes varies considerably among species, but the entire IGHV locus seems to be conserved in the subtelomeric or near-centromeric region of chromosome. The presence or absence of specific IGHV clan members and the lineage-specific expansion and contraction of IGHV genes indicate that the IGHV locus continues to evolve in a species-specific manner. Our results suggest that the evolution of IGHV multigene family is more complex than previously thought and that several factors may act synergistically for the development of antibody repertoire.