Expression Of Antigen Receptor Genes Research Articles

A move to exclude

It is not clear how lymphocytes establish monoallelic gene expression of antigen receptor genes. New data linking local chromatin modifications with nuclear movements provide a framework for deciphering this process.

Establishment of immune competence in the avian GALT during the immediate post-hatch period

Population dynamics of intestinal lymphocytes and the temporal development of lymphocyte functions were studied in broiler chicks during the first 2 weeks post-hatch. This period is of major immunological importance as the chick is immediately exposed to environmental antigens and pathogens. We show that the gut-associated lymphoid tissue contains functionally immature T and B lymphocytes at hatch, and that function is attained during the first 2 weeks of life as demonstrated by mRNA expression of both ChIL-2 and ChIFNγ. Functional maturation occurred in two stages: the first—during the first week post-hatch, and the second during the second week, which was also accompanied by an increase in lymphocyte population, as determined by expression of antigen receptor genes. Evidence is presented to show that in the intestinal milieu cellular immune responses mature earlier, and are a prerequisite for humoral responses. Hence, the lack of antibody response in young chicks is primarily due to immaturity of T lymphocytes.

Allelic exclusion of immunoglobulin gene rearrangement and expression: why and how?

Since the discovery of the allelic exclusion of immunoglobulin (Ig) gene expression by Pervis in the 1960s [ J. Exp. Med. 122 (1965) 853], much attention has been focused on its mechanism. Much less attention has been paid, however, to the question of why B cells demonstrate such unusual genetic regulation of antigen receptor gene expression. A large body of literature implicates the Ig gene products as feedback regulators of their own genetic rearrangement [ Adv. Immunol. 78 (2001) 169; Science 236 (1987) 816]. While a role for Ig gene products in the regulation of V(D)J recombination is beyond debate, it is extremely unlikely that such a feedback mechanism would be fast enough to avoid occasional near-simultaneous rearrangement of allelic loci leading to dual receptor gene expression. This review will suggest an hypothesis to answer the ‘why bother’ aspect of allelic exclusion and then go on to propose a mechanism, distinct from feedback regulation, which may contribute to the allelic exclusion of Ig gene expression.

Accessibility control of variable region gene assembly during T-cell development.

T-cell development is a complex and ordered process that is regulated in part by the progressive assembly and expression of antigen receptor genes. T cells can be divided into two lineages based on expression of either an alpha beta or gamma delta T-cell antigen receptor (TCR). The genes that encode the TCR beta and gamma chains lie in distinct loci, whereas the genes that encode the TCR alpha and delta chains lie in a single locus (TCR alpha/delta locus). Assembly of TCR variable region genes is mediated by a site-specific recombination process that is common among all lymphocytes. Despite the common nature of this process, recombination of TCR genes is tightly regulated within the context of the developing T cell. TCR beta, gamma and delta variable region genes are assembled prior to TCR alpha variable region genes. Furthermore, assembly of TCR beta variable region genes is regulated within the context of allelic exclusion. The regulation of rearrangement and expression of genes within the TCR alpha/delta locus presents a complicated problem. TCR alpha and delta variable region genes are assembled at different stages of T-cell development, and fully assembled TCR alpha and delta variable region genes must be expressed in distinct lineages of T cells, alpha beta and gamma delta, respectively. We have developed several experimental approaches to assess the role of cis-acting elements in regulating recombination and expression of TCR genes. Here we describe these approaches and discuss our analyses of the regulation of accessibility of the TCR beta and TCR alpha/delta loci during T-cell development.

Differential regulation of γ and δ T cell antigen receptor gene expression by phorbol esters and Ca2+ ionophores in the acute lymphocyte leukemia DND41 cell line

We have investigated the role of two signal transduction pathways on the regulation of the gamma and delta T cell antigen receptor (TcR) gene expression, in the acute lymphocytic leukemic cell line DND41. Protein kinase C (PKC) activation, and intracellular free Ca2+ mobilization, initiated by phorbol esters and calcium ionophores, respectively, not only acted independently but, more interestingly, their effects were antagonistic, suggesting a role for these signals during T cell differentiation. The Ca2+ ionophore, ionomycin, increased the levels of intracellular free Ca2+ and induced the expression of the gamma and delta chains of the T cell antigen receptor in a concentration-dependent manner. The phorbol ester 12-myristate 13-acetate down-regulated the basal gamma TcR expression with marginal effect on delta TcR mRNA, but diminished the induction of both gamma and delta TcR, initiated by the Ca2+ ionophore. These antagonistic effects of the two arms of the phospholipase C-mediated signal transduction pathways, i.e. PKC activation and increased intracellular free Ca2+, were specific to the regulation of the gamma and delta TcR, since the same signals exerted a synergistic effect on the mRNA levels of interleukin 2 receptor. These data confirm our hypothesis that the antagonistic regulation on the gamma and delta TcR gene expression by phorbol esters and calcium ionophores occurs in the same cell, and stresses the biological significance of PKC activation and intracellular free calcium mobilization during intrathymic differentiation and selection.

Genomic organization and expression of antigen receptor genes in murine lupus

Genomic organization and expression of antigen receptor genes in murine lupus

Activation of T cell antigen receptor alpha- and beta-chain genes in the thymus: implications for the lineages of developing cortical thymocytes.

Mammalian T lymphocytes mature in the thymus through a series of differentiation events that involve both rapid proliferation and extensive cell death. The mechanisms that govern these processes are currently unknown; however, both mitogenesis and death affect particular subpopulations of cells, suggesting the selective amplification and destruction of specific T cell clones. In mature peripheral T cells, proliferation is most commonly triggered by the recognition of antigen through the T cell antigen receptor complex. If antigen recognition also controls proliferation in the thymus, the differential expression of antigen receptor genes during maturation could play some role in determining the fate of developing T cells. In this study, we examined the expression of the alpha- and beta-chain genes of the T cell antigen receptor in different subpopulations of adult thymocytes. We compared two postmitotic populations--one that appears committed to die and one that appears mature--and several blast cell populations that are enriched for precursors of one or another presumptive lineage. We have found that Lyt-2-, L3T4- precursor thymocytes express much lower levels of both alpha- and beta-chain mRNA than the cells likely to be their immediate descendents. Furthermore, our results show that the cells of the major cortical lineage, which have at least a 95% probability of death, nevertheless express high levels of mature mRNA encoding both the alpha- and the beta-chains of the T cell antigen receptor. These results have important implications for the mechanisms involved in the overproduction and elimination of this major class of T lymphocyte.

The change of specificity, karyotype, and antigen-receptor gene expression is correlated in cytotoxic T-cell lines.

It has been postulated, that individual nontransformed vertebrate cells are limited to a finite number of mitotic divisions (Hayflick 1965). Beyond that physiological potential the cells either degenerate or transform malignantly. Long-term cultured T-cell clones are intriguing models to test the above postulate. Because of that model character, the karyotypic and molecular genetic analysis of cytotoxic lymphocyte clones (CTLL) and their variants should hint at the genetic and molecular events involved in changes of specificity and function, cellular instability and ultimately malignant transformation.