The Experts below are selected from a list of 33 Experts worldwide ranked by ideXlab platform

John F Kearney - One of the best experts on this subject based on the ideXlab platform.

  • Printed in Singapore Effects of IgM Allotype Suppression on Serum IgM Levels, B-1 and B-2 Cells, and Antibody Responses ir
    2013
    Co-Authors: Allotype Heterozygous, Ann Marie Hamilton, F Mice, John F Kearney
    Abstract:

    IgM Allotype heterozygous F1 mice were independently suppressed for Igh6a or Igh6b to evaluate the contribution of B-1 and B-2 cells to natural serum IgM levels and Ab responses. B-2 B cells expressing IgM of the suppressed Allotype were evident in the spleens of suppressed mice 4 to 6 weeks after cessation of the Suppression regimen, whereas B-1 B cells of the suppressed Allotype were undetectable for up to 9 months. Although serum IgM of the suppressed Allotype was initially depleted in mice suppressed for either Allotype, by 7 months of age, there were detectable levels of IgM of the suppressed Allotype in the serum; however, the levels were significantly below that found in nonsuppressed mice. When mice were immunized with either the T-independent or T-dependent form of phosphorylcholine, those suppressed for either Allotype, and consequently depleted of B-1 B cells of that Allotype, did not respond with phosphorylcholine-specific IgM of the suppressed Allotype. In contrast, when mice were immunized with 1-3 dextran, the Igh6a Allotype-suppressed mice were able to produce dextran-specific IgM of that Allotype. These results show that Allotype-bearing B-1 cells of both Allotypes can be effectively suppressed by this Suppression protocol and this produces long-lasting effects on B-1 cell levels and serum IgM of the suppressed Allotype. These observations reflect the derivation of the majority of B-1 cells from fetal-neonatal precursors, which cannot be replaced by newly emerging B-2 cells of adult origin. Their ablation by antibody treatment results in permanent alterations to the adult B-cell repertoire

  • effects of igm Allotype Suppression on serum igmlevels b 1 and b 2 cells and antibody responses irAllotype heterozygous f1 mice
    Developmental Immunology, 1994
    Co-Authors: Ann Marie Hamilton, John F Kearney
    Abstract:

    IgM Allotype heterozygous F1 mice were independently suppressed for Igh6a or Igh6b to evaluate the contribution of B-1 and B-2 cells to natural serum IgM levels and Ab responses. B-2 B cells expressing IgM of the suppressed Allotype were evident in the spleens of suppressed mice 4 to 6 weeks after cessation of the Suppression regimen, whereas B-1 B cells of the suppressed Allotype were undetectable for up to 9 months. Although serum IgM of the suppressed Allotype was initially depleted in mice suppressed for either Allotype, by 7 months of age, there were detectable levels of IgM of the suppressed Allotype in the serum; however, the levels were significantly below that found in nonsuppressed mice. When mice were immunized with either the T-independent or T-dependent form of phosphorylcholine, those suppressed for either Allotype, and consequently depleted of B-1 B cells of that Allotype, did not respond with phosphorylcholine-specific IgM of the suppressed Allotype. In contrast, when mice were immunized with α1-3 dextran, the Igh6a Allotype-suppressed mice were able to produce dextran-specific IgM of that Allotype. These results show that Allotype-bearing B-1 cells of both Allotypes can be effectively suppressed by this Suppression protocol and this produces long-lasting effects on B-1 cell levels and serum IgM of the suppressed Allotype. These observations reflect the derivation of the majority of B-1 cells from fetal-neonatal precursors, which cannot be replaced by newly emerging B-2 cells of adult origin. Their ablation by antibody treatment results in permanent alterations to the adult B-cell repertoire.

Guy Bordenave - One of the best experts on this subject based on the ideXlab platform.

  • Mechanisms of mouse T lymphocyte-induced Suppression of the IgG2ab Allotype and T lymphocyte tolerance to IgG2ab.
    Archivum immunologiae et therapiae experimentalis, 2001
    Co-Authors: Laleh Majlessi, Guy Bordenave
    Abstract:

    In mice of the Igha immunoglobulin allotypic haplotype we found, the presence of T lymphocytes with an inherent inhibitory activity against the expression of the IgG2a(b) Allotype (IgG2a of the Ighb immunoglobulin allotypic haplotype). This constitutive anti-IgG2a(b) T lymphocyte activity can be enhanced in vivo by what we called "sensitization", which usually consists of one or two intravenous injections of B splenocytes from Ighb congenic mice. When injected at birth, the resulting anti-IgG2a(b) T splenocytes induce, with 100% success, total, specific and chronic (but experimentally reversible) Suppression of IgG2a(b) in Igh(a/b) F1 hybrid mice prepared by mating Igh congenic mice. Even if restricted to IgG2a(b) expression, this experimental model, which deals with an unambiguous case of T cell-mediated down-regulation of immunoglobulin production, provides a clear and powerful tool to dissect finely the behavior of the partners (T and B lymphocytes) intervening in regulation within the immune system. For example, we observed that CD4 T lymphocytes were necessary to obtain full recruitment of anti-IgG2a(b) CD8 T lymphocytes during the sensitization, that Suppression induction in anti-IgG2a(b) T splenocytes of newborn recipients required cooperation between CD4 and CD8 T lymphocytes, and that CD8 T lymphocytes were essential for Suppression maintenance. We showed that this Suppression was not characterized by an accumulation of B lymphocytes containing the Allotype they could not secrete or Cgamma2a(b) mRNA they could not translate. The recipient's immune system was not involved in the suppession maintenance; this was done by donor T lymphocytes, which ensured the chronicity of IgG2a(b) Suppression throughout the recipient's life. We demonstrated that the mechanism of this Suppression implied an MHC-restricted presentation by target B lymphocytes of Cy2a(b) peptides to the T cell receptor (TCR) of anti-IgG2a(b) T lymphocytes. Notwithstanding the requirement of a CD4-CD8 T lymphocyte cooperation during the induction phase, we functionally determined that the Suppression induction implicated an MHC class I-, but not class II-restricted interaction. We also demonstrated the existence in vivo of alternative or concomitant use of perforine- and Fas-mediated cytotoxicity pathways in this T cell-induced IgG2a(b) Suppression. Thus this Suppression did not imply silencing IgG2a(b) production, but B lymphocyte destruction by CD8 T lymphocytes. Always using our Suppression model, we demonstrated that an agonistic anti-CD40 treatment helps in recruiting CD8 cytotoxic T lymphocytes, involved in immune regulatory functions and that CD40 expression on Ighb B lymphocytes confronted with CD8 T lymphocyte effectors only operating via the Fas pathway was involved in the total Suppression of IgG2a(b) expression. The selection and maintenance of such normal T cell activity against the IgG2a(b) Allotype in mice of different genetic backgrounds remain somewhat enigmatic. Indeed, we did not observe any similar activity against other immunoglobulin Allotypes or isotypes. The intestinal flora had no influence on the emergence of this anti-IgG2a(b) T lymphocyte activity, as it was untouched in germ-free-Igha mice when compared with normal Igha mice. More recently, this model offered an opportunity to study problems pertaining to immune tolerance. For instance, we showed that the genetic elements involved in the building of anti-IgG2a(b) TCR were available in Igha and Ighb mice of different genetic backgrounds, but that somatic constraints, namely the perinatal presence of IgG2a(b), effectively prevented their acquisition, while its absence led to their spontaneous emergence. Consequently, we were able to induce anti-IgG2a(b) T lymphocytes into a tolerance state by injecting Igha mice with soluble IgG2a(b) during the perinatal period. However, the full T lymphocyte tolerance obtained in this manner was not definitively acquired, as it had reversed spontaneously when investigated 3 to 6 months after the end of tolerogen treatment, even when this treatment had been prolonged from the perinatal period to 9 months of age. The mechanisms (induction and reversion) of this tolerance involves the physical elimination or the irreversible inactivation of the natural anti-IgG2a(b) T lymphocyte clones and their resurgence, from bone-marrow precursors, as long as the thymus remains operational, but not the establishment of a reversible, functional unresponsiveness (anergy) or an active, cell-mediated inhibition of anti-IgG2a(b) T clones. We attempted to elucidate, in Ighb mice, whether the natural T lymphocyte unresponsiveness to IgG2a(b) involved a central tolerance mechanism and to identify the type of tolerogen implicated in this tolerogenesis. The experiments principally showed that this natural T lymphocyte tolerance to IgG2a(b) was mediated by a thymic mechanism; that the capacity to induce it was gradually acquired by Ighb thymuses and was most probably due to potentially IgG2a(b)-producing/presenting cells, progressively colonizing the developing thymus; and that a significantly decreased postnatal Cy2a(b) gene transcription correlated with the emergence of anti-IgG2a(b) T lymphocytes in Igh(a/b) F1 (postnatally deprived of their B lymphocyte compartment), which subjected them to autoimmune IgG2a(b)-Allotype Suppression.

  • role of cd4 and cd8 cell subsets during amplification of natural t cell activity against igg2ab in igha mice and during induction of igg2ab Allotype Suppression in igha b mice
    Journal of Immunology, 1993
    Co-Authors: Laleh Majlessi, P Benaroch, C Denoyelle, Guy Bordenave
    Abstract:

    Transfer into F1 Igha/b mice of splenocytes from Igha mice sensitized once against B cells from an Ighb congenic strain induces total, chronic, and IgG2ab (IgG2a of the Ighb haplotype)-specific Allotype Suppression in these recipients. We previously demonstrated that both the CD4+ and CD8+ T subsets were necessary for inducing Suppression, but that CD8+, cells by themselves were sufficient for maintaining Suppression. We have studied the Suppression induction capacity of different mixtures of CD4+ and CD8+ subsets obtained by in vitro cytotoxic treatment of T splenocytes from normal or sensitized Igha mice, and we have established that Suppression induction requires the cooperation between CD4+ and CD8+ populations, both of which have to be IgG2ab specific. In addition, Igha mice were sensitized in the absence of CD4+ or CD8+ cells by in vivo cytotoxic treatment performed before and after the sensitization in order to obtain an IgG2ab-specific CD4+ population that has arisen in the absence of CD8+ cells, and vice versa. We found that only IgG2ab-specific CD4+ cells from anti-CD8-treated mice (T'sens CD4+) had the ability to induce Suppression in F1 Igha/b hosts. Nevertheless, the real effector cells in this Suppression model display the CD8+ phenotype, as in vivo cytotoxic anti-CD8 treatment of Igha/b recipients of T'sens CD4+ abrogates the Suppression induction capacity. Taken together, these results show that T'sens CD4+ have an important capacity to recruit CD8+ anti-IgG2ab effector cells from precursors that have been transferred with them into Igha/b hosts. These precursors are actually derived from the T'sens CD4+ cell preparation, because we have recently demonstrated that Suppression is maintained by donor T cells throughout the recipient's life. CD4+ cells can have their anti-IgG2ab activity amplified only by means of target cells (i.e., B cells from Ighb congenic mice), whereas, in the absence of CD4+ cells, and despite the presence of target cells, CD8+ cells seem unable to acquire this amplified activity.

Ann Marie Hamilton - One of the best experts on this subject based on the ideXlab platform.

  • Printed in Singapore Effects of IgM Allotype Suppression on Serum IgM Levels, B-1 and B-2 Cells, and Antibody Responses ir
    2013
    Co-Authors: Allotype Heterozygous, Ann Marie Hamilton, F Mice, John F Kearney
    Abstract:

    IgM Allotype heterozygous F1 mice were independently suppressed for Igh6a or Igh6b to evaluate the contribution of B-1 and B-2 cells to natural serum IgM levels and Ab responses. B-2 B cells expressing IgM of the suppressed Allotype were evident in the spleens of suppressed mice 4 to 6 weeks after cessation of the Suppression regimen, whereas B-1 B cells of the suppressed Allotype were undetectable for up to 9 months. Although serum IgM of the suppressed Allotype was initially depleted in mice suppressed for either Allotype, by 7 months of age, there were detectable levels of IgM of the suppressed Allotype in the serum; however, the levels were significantly below that found in nonsuppressed mice. When mice were immunized with either the T-independent or T-dependent form of phosphorylcholine, those suppressed for either Allotype, and consequently depleted of B-1 B cells of that Allotype, did not respond with phosphorylcholine-specific IgM of the suppressed Allotype. In contrast, when mice were immunized with 1-3 dextran, the Igh6a Allotype-suppressed mice were able to produce dextran-specific IgM of that Allotype. These results show that Allotype-bearing B-1 cells of both Allotypes can be effectively suppressed by this Suppression protocol and this produces long-lasting effects on B-1 cell levels and serum IgM of the suppressed Allotype. These observations reflect the derivation of the majority of B-1 cells from fetal-neonatal precursors, which cannot be replaced by newly emerging B-2 cells of adult origin. Their ablation by antibody treatment results in permanent alterations to the adult B-cell repertoire

  • effects of igm Allotype Suppression on serum igmlevels b 1 and b 2 cells and antibody responses irAllotype heterozygous f1 mice
    Developmental Immunology, 1994
    Co-Authors: Ann Marie Hamilton, John F Kearney
    Abstract:

    IgM Allotype heterozygous F1 mice were independently suppressed for Igh6a or Igh6b to evaluate the contribution of B-1 and B-2 cells to natural serum IgM levels and Ab responses. B-2 B cells expressing IgM of the suppressed Allotype were evident in the spleens of suppressed mice 4 to 6 weeks after cessation of the Suppression regimen, whereas B-1 B cells of the suppressed Allotype were undetectable for up to 9 months. Although serum IgM of the suppressed Allotype was initially depleted in mice suppressed for either Allotype, by 7 months of age, there were detectable levels of IgM of the suppressed Allotype in the serum; however, the levels were significantly below that found in nonsuppressed mice. When mice were immunized with either the T-independent or T-dependent form of phosphorylcholine, those suppressed for either Allotype, and consequently depleted of B-1 B cells of that Allotype, did not respond with phosphorylcholine-specific IgM of the suppressed Allotype. In contrast, when mice were immunized with α1-3 dextran, the Igh6a Allotype-suppressed mice were able to produce dextran-specific IgM of that Allotype. These results show that Allotype-bearing B-1 cells of both Allotypes can be effectively suppressed by this Suppression protocol and this produces long-lasting effects on B-1 cell levels and serum IgM of the suppressed Allotype. These observations reflect the derivation of the majority of B-1 cells from fetal-neonatal precursors, which cannot be replaced by newly emerging B-2 cells of adult origin. Their ablation by antibody treatment results in permanent alterations to the adult B-cell repertoire.

Laleh Majlessi - One of the best experts on this subject based on the ideXlab platform.

  • Mechanisms of mouse T lymphocyte-induced Suppression of the IgG2ab Allotype and T lymphocyte tolerance to IgG2ab.
    Archivum immunologiae et therapiae experimentalis, 2001
    Co-Authors: Laleh Majlessi, Guy Bordenave
    Abstract:

    In mice of the Igha immunoglobulin allotypic haplotype we found, the presence of T lymphocytes with an inherent inhibitory activity against the expression of the IgG2a(b) Allotype (IgG2a of the Ighb immunoglobulin allotypic haplotype). This constitutive anti-IgG2a(b) T lymphocyte activity can be enhanced in vivo by what we called "sensitization", which usually consists of one or two intravenous injections of B splenocytes from Ighb congenic mice. When injected at birth, the resulting anti-IgG2a(b) T splenocytes induce, with 100% success, total, specific and chronic (but experimentally reversible) Suppression of IgG2a(b) in Igh(a/b) F1 hybrid mice prepared by mating Igh congenic mice. Even if restricted to IgG2a(b) expression, this experimental model, which deals with an unambiguous case of T cell-mediated down-regulation of immunoglobulin production, provides a clear and powerful tool to dissect finely the behavior of the partners (T and B lymphocytes) intervening in regulation within the immune system. For example, we observed that CD4 T lymphocytes were necessary to obtain full recruitment of anti-IgG2a(b) CD8 T lymphocytes during the sensitization, that Suppression induction in anti-IgG2a(b) T splenocytes of newborn recipients required cooperation between CD4 and CD8 T lymphocytes, and that CD8 T lymphocytes were essential for Suppression maintenance. We showed that this Suppression was not characterized by an accumulation of B lymphocytes containing the Allotype they could not secrete or Cgamma2a(b) mRNA they could not translate. The recipient's immune system was not involved in the suppession maintenance; this was done by donor T lymphocytes, which ensured the chronicity of IgG2a(b) Suppression throughout the recipient's life. We demonstrated that the mechanism of this Suppression implied an MHC-restricted presentation by target B lymphocytes of Cy2a(b) peptides to the T cell receptor (TCR) of anti-IgG2a(b) T lymphocytes. Notwithstanding the requirement of a CD4-CD8 T lymphocyte cooperation during the induction phase, we functionally determined that the Suppression induction implicated an MHC class I-, but not class II-restricted interaction. We also demonstrated the existence in vivo of alternative or concomitant use of perforine- and Fas-mediated cytotoxicity pathways in this T cell-induced IgG2a(b) Suppression. Thus this Suppression did not imply silencing IgG2a(b) production, but B lymphocyte destruction by CD8 T lymphocytes. Always using our Suppression model, we demonstrated that an agonistic anti-CD40 treatment helps in recruiting CD8 cytotoxic T lymphocytes, involved in immune regulatory functions and that CD40 expression on Ighb B lymphocytes confronted with CD8 T lymphocyte effectors only operating via the Fas pathway was involved in the total Suppression of IgG2a(b) expression. The selection and maintenance of such normal T cell activity against the IgG2a(b) Allotype in mice of different genetic backgrounds remain somewhat enigmatic. Indeed, we did not observe any similar activity against other immunoglobulin Allotypes or isotypes. The intestinal flora had no influence on the emergence of this anti-IgG2a(b) T lymphocyte activity, as it was untouched in germ-free-Igha mice when compared with normal Igha mice. More recently, this model offered an opportunity to study problems pertaining to immune tolerance. For instance, we showed that the genetic elements involved in the building of anti-IgG2a(b) TCR were available in Igha and Ighb mice of different genetic backgrounds, but that somatic constraints, namely the perinatal presence of IgG2a(b), effectively prevented their acquisition, while its absence led to their spontaneous emergence. Consequently, we were able to induce anti-IgG2a(b) T lymphocytes into a tolerance state by injecting Igha mice with soluble IgG2a(b) during the perinatal period. However, the full T lymphocyte tolerance obtained in this manner was not definitively acquired, as it had reversed spontaneously when investigated 3 to 6 months after the end of tolerogen treatment, even when this treatment had been prolonged from the perinatal period to 9 months of age. The mechanisms (induction and reversion) of this tolerance involves the physical elimination or the irreversible inactivation of the natural anti-IgG2a(b) T lymphocyte clones and their resurgence, from bone-marrow precursors, as long as the thymus remains operational, but not the establishment of a reversible, functional unresponsiveness (anergy) or an active, cell-mediated inhibition of anti-IgG2a(b) T clones. We attempted to elucidate, in Ighb mice, whether the natural T lymphocyte unresponsiveness to IgG2a(b) involved a central tolerance mechanism and to identify the type of tolerogen implicated in this tolerogenesis. The experiments principally showed that this natural T lymphocyte tolerance to IgG2a(b) was mediated by a thymic mechanism; that the capacity to induce it was gradually acquired by Ighb thymuses and was most probably due to potentially IgG2a(b)-producing/presenting cells, progressively colonizing the developing thymus; and that a significantly decreased postnatal Cy2a(b) gene transcription correlated with the emergence of anti-IgG2a(b) T lymphocytes in Igh(a/b) F1 (postnatally deprived of their B lymphocyte compartment), which subjected them to autoimmune IgG2a(b)-Allotype Suppression.

  • role of cd4 and cd8 cell subsets during amplification of natural t cell activity against igg2ab in igha mice and during induction of igg2ab Allotype Suppression in igha b mice
    Journal of Immunology, 1993
    Co-Authors: Laleh Majlessi, P Benaroch, C Denoyelle, Guy Bordenave
    Abstract:

    Transfer into F1 Igha/b mice of splenocytes from Igha mice sensitized once against B cells from an Ighb congenic strain induces total, chronic, and IgG2ab (IgG2a of the Ighb haplotype)-specific Allotype Suppression in these recipients. We previously demonstrated that both the CD4+ and CD8+ T subsets were necessary for inducing Suppression, but that CD8+, cells by themselves were sufficient for maintaining Suppression. We have studied the Suppression induction capacity of different mixtures of CD4+ and CD8+ subsets obtained by in vitro cytotoxic treatment of T splenocytes from normal or sensitized Igha mice, and we have established that Suppression induction requires the cooperation between CD4+ and CD8+ populations, both of which have to be IgG2ab specific. In addition, Igha mice were sensitized in the absence of CD4+ or CD8+ cells by in vivo cytotoxic treatment performed before and after the sensitization in order to obtain an IgG2ab-specific CD4+ population that has arisen in the absence of CD8+ cells, and vice versa. We found that only IgG2ab-specific CD4+ cells from anti-CD8-treated mice (T'sens CD4+) had the ability to induce Suppression in F1 Igha/b hosts. Nevertheless, the real effector cells in this Suppression model display the CD8+ phenotype, as in vivo cytotoxic anti-CD8 treatment of Igha/b recipients of T'sens CD4+ abrogates the Suppression induction capacity. Taken together, these results show that T'sens CD4+ have an important capacity to recruit CD8+ anti-IgG2ab effector cells from precursors that have been transferred with them into Igha/b hosts. These precursors are actually derived from the T'sens CD4+ cell preparation, because we have recently demonstrated that Suppression is maintained by donor T cells throughout the recipient's life. CD4+ cells can have their anti-IgG2ab activity amplified only by means of target cells (i.e., B cells from Ighb congenic mice), whereas, in the absence of CD4+ cells, and despite the presence of target cells, CD8+ cells seem unable to acquire this amplified activity.

L. Adler - One of the best experts on this subject based on the ideXlab platform.

  • A ROLE FOR CLONAL DOMINANCE IN THE MAINTENANCE OF Allotype Suppression?*
    2013
    Co-Authors: A Yamada, Louise T. Adler, L. Adler
    Abstract:

    Allotype Suppression in the rabbit is characterized by a deficiency in immunoglobulin of a particular Allotype and a compensatory increase in immunoglobulin carrying an alternate allotypic marker (1). Suppression is induced by perinatal treatment of the animal with antibody specific for the Allotype that is to be suppressed, and it is perpetuated for months or years by mechanisms that remain to be elucidated. Among the possible causes of the lasting Suppression are clonal elimination as a direct consequence of the treatment used in the induction of Suppression, and an active autoimmune response that follows the phase of passive Suppression and which might be mediated by specific suppressor cells. Although the former possibility has not been totally eliminated as a contributing factor in the early stages of Suppression, there exists no evidence for cytotoxicity of anti-allotypic antibodies, and this mechanism would not explain an important attribute of chronic Suppression, namely the increasing number of cells bearing the suppressed Allotype on their membranes during a period when serum concentrations of the suppressed Allotype remain profoundly depressed (2)

  • III. IN VITRO STUDIES ON Allotype Suppression Components of AntiAllotype Serum Active in Release from Allotype Suppression*
    2013
    Co-Authors: T. Adler, L. Adler
    Abstract:

    In rabbits which are heterogeneous with respect to antigenic determinants on serum immunoglobulins (Ig), prenatal or neonatal exposure to antibodies specific for one allelic Allotype leads to a long-lasting Suppression of that type with compensatory production of the alternate allelic product. This phenomenon, called Allotype Suppression, was first described by Dray in 1962 (1). Although many studies since then have amply verified and further characterized Dray's original observations (reviewed by Mage in reference 2), the mechanism of Suppression remains obscure. By using specific antiAllotype sera it has been possible to identify b locus determinants on T2-neutralizing antibodies formed by spleen cells of heterozygous rabbits in vitro and to demonstrate that cells from b4b5 rabbits which were deficient in their ability to produce b4 Ig because of exposure to anti-b4 in utero formed anti-T2 antibodies which appeared to be entirely of the nonsuppressed type, namely, b5 (3). However, when such cells were cultured in the presence of anti-b5 serum made in b4 rabbits, b5 anti-T2 production was suppressed, while highly significant amounts of b4 anti-T2 wer