China
Africa
Explore chapters and articles related to this topic
Gene Rearrangement in Leukemias and Lymphomas
Published in John T. Kemshead, Pediatric Tumors: Immunological and Molecular Markers, 2020
CD7-positive blast cells are identified in approximately 20% of childhood ALL cases which are, therefore, classified as T-ALLs.33 Rearranged Cβ and germline Ig genes have been observed in the majority of cases analyzed.15,16,22,68–72 Although it has been suggested that the patterns of CP rearrangement in T-ALL are nonrandom, other authors have published data which refute this hypothesis.22,68,71,72 Two cases have been reported in which the mediastinal mass typical of T-ALL was present but the immunological profiles were inconsistent with this diagnosis.73 Genetic analysis demonstrated IgH rearrangement: the Cβ genes were not examined. Rearranged Cβ and IgH genes have been detected in approximately 10% of T-ALLs studied.16,20,21,68,70,71 The configurations of the TCR Cβ and Ig genes have been examined in 39 cases of childhood non-T, non-B ALL.72 IgH rearrangement was detected in all cases but 25% of the series also exhibited nongermline Cβ gene configurations. There were no other indications that these ten patients differed from the rest of the group and only clinical follow up will reveal the significance, if any, of this finding. The reason why both gene systems undergo somatic recombination in certain cases of malignancies is unknown: it may reflect errors which occur in normal lymphocytes at a low frequency, or it may be connected with the neoplastic process.
Autoimmunity and Immune Pathological Aspects of Virus Disease
Published in Irun R. Cohen, Perspectives on Autoimmunity, 2020
H. Wege, R. Dörries, P. Massa, R. Watanabe
Discrimination between self and non-self requires interaction of the diversifying B-cell repertoire with T-cells responsible for regulatory functions. The basis for the enormous flexibility of possible antibody responses is the existence of many B-cells precursor germ lines which acquire their final antigen specifity by somatic recombination and rearrangements of multiple gene segments coding for the immunoglobulin heavy and light chain molecules.115 In addition to the many combinations of germ line gene segments, point mutations can occur during clonal expansion and thus greatly enhance the potential antibody repertoire of the individual organism. Induction of mature B-cell clones to proliferate and to produce antibodies requires several steps triggered by binding of specific antigen as well as factors produced by macrophages and antigen-specific T-lymphocytes (so-called helper or inducer T-cells). Similar principles are true for activation of cytotoxic effector T-cells.116
Dopamine in the Immune and Hematopoietic Systems
Published in Nira Ben-Jonathan, Dopamine, 2020
T cells are created by lymphopoiesis from a common lymphoid progenitor in the bone marrow. The newly generated cells migrate to the thymus where they undergo extensive maturation and screening. Through a combination of positive and negative selection processes, the cells are differentiated, yielding a repertoire of mature T cells that tolerate self-antigens and are capable of mounting strong responses to foreign antigens. Within the thymus, T cells undergo a V(D)J recombination, a unique mechanism of genetic recombination that occurs only in developing lymphocytes during maturation. It involves somatic recombination that results in a highly diverse assortment of the TCRs. Cell selection in the thymus is accompanied by an extensive cell death by apoptosis and phagocytosis, with only a very small percent of the cells surviving the selection process, and these are exported to extra-thymic sites.
B cells and upper airway disease: allergic rhinitis and chronic rhinosinusitis with nasal polyps evaluated
Published in Expert Review of Clinical Immunology, 2021
Harsha H Kariyawasam, Louisa K James
Early B-cell development occurs in bone marrow where the immunoglobulin variable gene is generated by somatic recombination of V (variable) D (diversity) J (joining) segments at the heavy-chain locus and VJ segments at the light-chain locus. The breath-taking diversity of the variable regions is created through the random rearrangement of these gene segments and is further increased by deletion or insertion of nucleotides at the junctions during recombination. It is estimated that the antigen-naïve repertoires could theoretically exceed 1016 variants [35] and in practical terms means that each newly generated B cell has an entirely unique antigen-binding site. Positive selection of immature B cells expressing a functional BCR on their surface permits their exit out of the bone marrow and into the periphery. Further maturation of immature B cells through two distinct transitional stages occurs prior to their commitment to either the follicular or marginal zone B fate, thought to depend in part on the strength of signaling through the BCR [36]. Marginal zone B cells largely reside within discrete spatial regions of secondary lymphoid tissue such as the spleen. They are innate-like B cells important for generating immunity to blood-borne bacterial antigens through rapid production of antibody [37]. The majority of immature B cells become follicular B cells which recirculate through SLOs until they become activated following antigen encounter.
TCR sequencing analysis of cancer tissues and tumor draining lymph nodes in colorectal cancer patients
Published in OncoImmunology, 2019
Tatsuo Matsuda, Eisaku Miyauchi, Yu-Wen Hsu, Satoshi Nagayama, Kazuma Kiyotani, Makda Zewde, Jae-Hyun Park, Taigo Kato, Makiko Harada, Shimpei Matsui, Masashi Ueno, Kazumasa Fukuda, Nobuaki Suzuki, Shoichi Hazama, Hiroaki Nagano, Hiroya Takeuchi, Wickii T. Vigneswaran, Yuko Kitagawa, Yusuke Nakamura
T cell receptors (TCR), most of which consists of TCR alpha (TCRα) and beta (TCRβ) chains, are expressed on T cells and recognize antigens presented on the major histocompatibility complex (MHC) molecules.14 To recognize a large variety of antigens, TCR genes undergo the somatic recombination process of variable (V), diversity (D) (for beta chain), and joining (J) exons, termed the V(D)J recombination, and generate an extremely high degree of the diversity. We established next-generation sequencing-based TCR repertoire analysis using mRNAs and applied our technology for the TCR analysis of various types of tumor.15-21 A detailed TCR transcript analysis has provided a new insight into T cell responses in various disease conditions including characterization of the tumor microenvironment.
Systematic in vivo study of NiO nanowires and nanospheres: biodegradation, uptake and biological impacts
Published in Nanotoxicology, 2018
Mohamed Alaraby, Alba Hernández, Ricard Marcos
One of the most harmful effects that NM can induce in the exposed organisms is to damage the genetic material. In fact, oxidative DNA damage is the inevitable end after the oxidative stress induced by NM exposure. Due to the relevance of this end-point, two important genotoxicity assays were used. The comet assay primarily detects DNA damage, mainly in the form of DNA breaks. The somatic mutation and recombination test (SMART-assay) detects fixed DNA damage induced by different mechanisms, including somatic recombination. As observed, all Ni compounds were able to induce DNA breaks in a dose-dependent manner, reaching high significance at the highest exposure dose (10 mM) (Figure 11(A)). On the contrary, all tested Ni compounds failed to induce gene mutations at any of the selected exposure doses (Figure 11(B)).