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  • 1
    Language: English
    In: Annals of the New York Academy of Sciences, January 2011, Vol.1217, pp.32-44
    Description: Effective B cell-mediated immunity, including the formation of germinal centers and the generation of high-affinity memory B cells and long-lived plasma cells, is dependent on CD4(+) T cells. Immunodeficiencies that present with defects in the antibody response have provided insights into the molecular mechanisms of B cell responses and the provision of T cell help. One such immunodeficiency is X-linked lymphoproliferative disease (XLP), which results from mutations in SH2D1A, the gene encoding SLAM-associated protein (SAP). Patients with XLP present with humoral defects characterized by hypogammaglobulinemia. We now know that SAP, through its signaling downstream of multiple members of the signaling lymphocytic activation molecule (SLAM) family of cell surface receptors, plays a crucial role in many aspects of this immune response. Here, we discuss the role of SAP in the generation of humoral immunity, particularly T cell-dependent antibody responses and the generation of germinal centers.
    Keywords: Immunity, Humoral ; Antigens, CD -- Physiology ; Intracellular Signaling Peptides and Proteins -- Physiology ; Receptors, Cell Surface -- Physiology
    E-ISSN: 1749-6632
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  • 2
    In: Nature, 2016
    Description: Although T cells are known to fight chronic viral infections, the exact requirements for this process have been a mystery. Papers in this issue by Im et al.1 (page 417) and He et al.2 (page 412) and in Nature Immunology by Leong et al.3 have identified a population of T cells that express the CXCR5 and...
    Keywords: Viral Infections ; Viruses ; Immunology ; Cytotoxicity ; Lymphocytes;
    ISSN: 0028-0836
    E-ISSN: 1476-4687
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  • 3
    Language: English
    In: Annals of the New York Academy of Sciences, Jan, 2011, Vol.1217, p.32(13)
    Description: To authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1749-6632.2010.05824.x Byline: Cindy S. Ma (12), Elissa K. Deenick (12) Keywords: SAP; SLAM family; germinal center; T follicular helper cell; antibody Abstract: Effective B cell-mediated immunity, including the formation of germinal centers and the generation of high-affinity memory B cells and long-lived plasma cells, is dependent on CD4.sup.+ T cells. Immunodeficiencies that present with defects in the antibody response have provided insights into the molecular mechanisms of B cell responses and the provision of T cell help. One such immunodeficiency is X-linked lymphoproliferative disease (XLP), which results from mutations in SH2D1A, the gene encoding SLAM-associated protein (SAP). Patients with XLP present with humoral defects characterized by hypogammaglobulinemia. We now know that SAP, through its signaling downstream of multiple members of the signaling lymphocytic activation molecule (SLAM) family of cell surface receptors, plays a crucial role in many aspects of this immune response. Here, we discuss the role of SAP in the generation of humoral immunity, particularly T cell-dependent antibody responses and the generation of germinal centers. Author Affiliation: (1)Immunology Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia. (2)St Vincent's Clinical School, University of NSW, Kensington, NSW, Australia Article note: Address for correspondence: Elissa Deenick, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia. e.deenick@garvan.org.au
    Keywords: T Cells ; Software Industry ; Immunodeficiency ; Immune Response
    ISSN: 0077-8923
    Source: Cengage Learning, Inc.
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  • 4
    Language: English
    In: Annals of the New York Academy of Sciences, Jan, 2011, Vol.1217, p.32(13)
    Description: To authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1749-6632.2010.05824.x Byline: Cindy S. Ma (12), Elissa K. Deenick (12) Keywords: SAP; SLAM family; germinal center; T follicular helper cell; antibody Abstract: Effective B cell-mediated immunity, including the formation of germinal centers and the generation of high-affinity memory B cells and long-lived plasma cells, is dependent on CD4.sup.+ T cells. Immunodeficiencies that present with defects in the antibody response have provided insights into the molecular mechanisms of B cell responses and the provision of T cell help. One such immunodeficiency is X-linked lymphoproliferative disease (XLP), which results from mutations in SH2D1A, the gene encoding SLAM-associated protein (SAP). Patients with XLP present with humoral defects characterized by hypogammaglobulinemia. We now know that SAP, through its signaling downstream of multiple members of the signaling lymphocytic activation molecule (SLAM) family of cell surface receptors, plays a crucial role in many aspects of this immune response. Here, we discuss the role of SAP in the generation of humoral immunity, particularly T cell-dependent antibody responses and the generation of germinal centers. Author Affiliation: (1)Immunology Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia. (2)St Vincent's Clinical School, University of NSW, Kensington, NSW, Australia Article note: Address for correspondence: Elissa Deenick, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia. e.deenick@garvan.org.au
    Keywords: T Cells ; Software Industry ; Immunodeficiency ; Immune Response
    ISSN: 0077-8923
    Source: Cengage Learning, Inc.
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  • 5
    Language: English
    In: Annals of the New York Academy of Sciences, Feb, 2012, Vol.1250, p.1(13)
    Description: To authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1749-6632.2011.06361.x Byline: Stuart G. Tangye (12), Elissa K. Deenick (12), Umaimainthan Palendira (12), Cindy S. Ma (12) Keywords: immunodeficiency; T follicular helper cells; T-dependent B cell activation; T-B cell interactions; humoral immunity; XLP Abstract: Regulated interactions between cells of the immune system facilitate the generation of successful immune responses, thereby enabling efficient neutralization and clearance of pathogens and the establishment of both cell- and humoral-mediated immunological memory. The corollary of this is that impediments to efficient cell-cell interactions, normally necessary for differentiation and effector functions of immune cells, underly the clinical features and disease pathogenesis of primary immunodeficiencies. In affected individuals, these defects manifest as impaired long-term humoral immunity and susceptibility to infection by specific pathogens. In this review, we discuss the importance of, and requirements for, effective interactions between B cells and T cells during the formation of CD4.sup.+ T follicular helper cells and the elicitation of cytotoxic function of virus-specific CD8.sup.+ T cells, as well as how these processes are abrogated in primary immunodeficiencies due to loss-of-function mutations in defined genes. Author Affiliation: (1)Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia. (2)St. Vincent's Clinical School, University of NSW, Sydney, NSW, Australia Article note: Address for correspondence: Dr. Stuart Tangye, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, 2010, NSW, Australia. s.tangye@garvan.org.au
    Keywords: Immunodeficiency ; Cells (Biology) ; T Cells ; Disease Susceptibility
    ISSN: 0077-8923
    Source: Cengage Learning, Inc.
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  • 6
    Language: English
    In: Annals of the New York Academy of Sciences, Feb, 2012, Vol.1250, p.1(13)
    Description: To authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1749-6632.2011.06361.x Byline: Stuart G. Tangye (12), Elissa K. Deenick (12), Umaimainthan Palendira (12), Cindy S. Ma (12) Keywords: immunodeficiency; T follicular helper cells; T-dependent B cell activation; T-B cell interactions; humoral immunity; XLP Abstract: Regulated interactions between cells of the immune system facilitate the generation of successful immune responses, thereby enabling efficient neutralization and clearance of pathogens and the establishment of both cell- and humoral-mediated immunological memory. The corollary of this is that impediments to efficient cell-cell interactions, normally necessary for differentiation and effector functions of immune cells, underly the clinical features and disease pathogenesis of primary immunodeficiencies. In affected individuals, these defects manifest as impaired long-term humoral immunity and susceptibility to infection by specific pathogens. In this review, we discuss the importance of, and requirements for, effective interactions between B cells and T cells during the formation of CD4.sup.+ T follicular helper cells and the elicitation of cytotoxic function of virus-specific CD8.sup.+ T cells, as well as how these processes are abrogated in primary immunodeficiencies due to loss-of-function mutations in defined genes. Author Affiliation: (1)Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia. (2)St. Vincent's Clinical School, University of NSW, Sydney, NSW, Australia Article note: Address for correspondence: Dr. Stuart Tangye, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, 2010, NSW, Australia. s.tangye@garvan.org.au
    Keywords: Immunodeficiency ; Cells (Biology) ; T Cells ; Disease Susceptibility
    ISSN: 0077-8923
    Source: Cengage Learning, Inc.
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  • 7
    In: Annals of the New York Academy of Sciences, February 2012, Vol.12501(1), pp.1-13
    Description: Regulated interactions between cells of the immune system facilitate the generation of successful immune responses, thereby enabling efficient neutralization and clearance of pathogens and the establishment of both cell‐ and humoral‐mediated immunological memory. The corollary of this is that impediments to efficient cell–cell interactions, normally necessary for differentiation and effector functions of immune cells, underly the clinical features and disease pathogenesis of primary immunodeficiencies. In affected individuals, these defects manifest as impaired long‐term humoral immunity and susceptibility to infection by specific pathogens. In this review, we discuss the importance of, and requirements for, effective interactions between B cells and T cells during the formation of CD4 T follicular helper cells and the elicitation of cytotoxic function of virus‐specific CD8 T cells, as well as how these processes are abrogated in primary immunodeficiencies due to loss‐of‐function mutations in defined genes.
    Keywords: Immunodeficiency ; T Follicular Helper Cells ; T‐Dependent B Cell Activation ; T–B Cell Interactions ; Humoral Immunity ; Xlp
    ISSN: 0077-8923
    E-ISSN: 1749-6632
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  • 8
    Language: English
    In: The Journal of clinical investigation, November 2013, Vol.123(11), pp.4781-5
    Description: Approximately 90% of patients with isolated agammaglobulinemia and failure of B cell development have mutations in genes required for signaling through the pre–B cell and B cell receptors. The nature of the gene defect in the majority of remaining patients is unknown. We recently identified 4 patients with agammaglobulinemia and markedly decreased numbers of peripheral B cells. The B cells that could be detected had an unusual phenotype characterized by the increased expression of CD19 but the absence of a B cell receptor. Genetic studies demonstrated that all 4 patients had the exact same de novo mutation in the broadly expressed transcription factor E47. The mutant protein (E555K) was stable in patient-derived EBV-transformed cell lines and cell lines transfected with expression vectors. E555K in the transfected cells localized normally to the nucleus and resulted in a dominant negative effect when bound to DNA as a homodimer with wild-type E47. Mutant E47 did permit DNA binding by a tissue-specific heterodimeric DNA-binding partner, myogenic differentiation 1 (MYOD). These findings document a mutational hot-spot in E47 and represent an autosomal dominant form of agammaglobulinemia. Further, they indicate that E47 plays a critical role in enforcing the block in development of B cell precursors that lack functional antigen receptors.
    Keywords: Mutation, Missense ; Agammaglobulinemia -- Genetics ; B-Lymphocytes -- Immunology ; Basic Helix-Loop-Helix Transcription Factors -- Genetics ; Receptors, Antigen, B-Cell -- Deficiency
    ISSN: 00219738
    E-ISSN: 1558-8238
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  • 9
    In: Pathology, 2015, Vol.47 Abstracts: RCPA Pathology Update 2015 IAP Australasian Division 39th Annual Scientific Meeting, pp.S42-S42
    Description: The focus of our laboratory has been trying to decipher the development, differentiation and function of B and T cells in humans. We do this by studying these lymphocyte populations in primary immunodeficiencies (PIDs) due to monogenic mutations in critical genes. During the course of our study of PIDs, it has become evident that different cohorts of patients display distinct B and/or T cell phenotypes that are often diagnostic even prior to the discovery of the genetic lesion. For example X-linked lymphoproliferative disease (XLP) is a rare primary immunodeficiency due to mutations in SH2D1A encoding the intracellular adaptor protein SAP. Clinically, XLP patients present with hypogammaglobulinaemia, fulminant infectious mononucleosis, and/or lymphoma. We have previously found SAP is required for the development of NKT cells, which in humans are defined as CD3Va24Vb11 cells, and are absent in XLP patients. Furthermore, consistent with hypogammaglobulinaemia, the B cell compartment from XLP patients was found to have a severe reduction in CD27 memory B cells and Ig class switched cells. More recently we have developed an intracellular staining method for detecting SAP expression. In normal healthy donors SAP can be detected in T cells, but not B cells, as these cells do not express SAP. In XLP patients, SAP is absent in both the B and T cell compartments. Furthermore, XLP carriers can be readily identified, as due to random X-inactivation, they have T cells that are both SAP as well as SAP. Similarly, patients with loss of function mutations in STAT3 and DOCK8 present with a distinct lymphocyte phenotype, which can be readily revealed through flow cytometry-based assays; these will be further discussed.
    Keywords: Medicine ; Biology;
    ISSN: 1465-3931
    ISSN: 00313025
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  • 10
    Language: English
    In: Journal of Clinical Immunology, 2016, Vol.36(Supplement 1), pp.40-47
    Description: T follicular helper (Tfh) cells are a subset of effector CD4 + T cells specialised to induce Ab production by B cells. This review highlights some of the recent advances in the field of human Tfh cells that have come from the study of primary immunodeficiencies. In particular it is increasingly evident that the quality of the Tfh cells that are generated, is just as important as the quantity.
    Keywords: Human T follicular helper (Tfh) cells ; primary immunodeficiency ; B-cell help ; humoral immunity
    ISSN: 0271-9142
    E-ISSN: 1573-2592
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