Human T Cell Activation Induces the Expression of a Novel CD45 Isoform That Is Analogous to Murine B220 and Is Associated with Altered O-Glycan Synthesis and Onset of Apoptosis

doi:10.1006/cimm.2001.1865

Cellular Immunology

Volume 213, Issue 1, 10 October 2001, Pages 72-81

https://doi.org/10.1006/cimm.2001.1865 Get rights and content

Abstract

Activated T cells undergo changes during their transition to T cell blasts and, subsequently, via a phase of anergy, to apoptosis. For example, activated murine T cell blasts express the B-cell-specific CD45R isoform, B220, a marker also present on T cells in mice and humans with defective Fas-mediated apoptosis in vivo, suggesting a role for B220 up-regulation in the transition of activation to apoptosis. Human T cells, activated in vitro with superantigens and mitogens, also express B220 as they undergo blastogenesis and cell cycle progression. B220 expression peaks on T cells undergoing apoptosis. CD43-hexasaccharide glycoform expression and lectin binding profiles indicate that B220 expression is reflective of altered O-linked glycan biosynthesis found in specific T cell subsets transitioning through the phases of proliferation, anergy, and apoptosis. Potential implications of these alterations include changes in lymphocyte adhesion and trafficking and homeostasis through altered sensitivity to Fas-dependent and independent pathways of apoptosis.

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TCRαβ+CD3+CD4−CD8− (double negative) T cells in autoimmunity
2018, Autoimmunity Reviews
Citation Excerpt :
As DN T cells from Fas-deficient MRL.lpr mice, cells from ALPS patients abnormally express the B cell antigen B220, an isoform of the CD45 antigen (that used to be referred to as leukocyte common antigen; LCA) [99]. Of note, the B cell marker B220 is alternatively expressed on activated T cells that undergo apoptosis [100]. Furthermore, DN T cells from ALPS patients co-express CD27 and CD28 [101], a characteristic of naïve and central memory T cell subsets that is usually absent in effector T cells [102].
TCRαβ⁺CD3⁺CD4⁻CD8⁻ “double negative” (DN) T cells comprise a small subset of mature peripheral T cells. The origin and function of DN T cells are somewhat unclear and discussed controversially. While DN T cells resemble a rare and heterogeneous T cell subpopulation in healthy individuals, numbers of TCRαβ⁺ DN T cells are expanded in several inflammatory conditions, where they also exhibit distinct effector phenotypes and infiltrate inflamed tissues. Thus, DN T cells may be involved in systemic inflammation and tissue damage in autoimmune/inflammatory conditions, including SLE, Sjögren's syndrome, and psoriasis. Here, the current understanding of the origin and phenotype of DN T cells, and their role in the instruction of immune responses, autoimmunity and inflammation will be discussed in health and disease.
Expression of alternatively spliced CD45 isoforms by channel catfish clonal T and B cells is dependent on activation state of the cell and regulated by protein synthesis and degradation
2010, Developmental and Comparative Immunology
In mammals, expression of the three alternatively spliced exons of the tyrosine phosphatase CD45 is regulated by the developmental and activation state of the cell. In comparison, the channel catfish, Ictalurus punctatus, CD45 homolog contains 18 functional alternatively spliced exons. Since very little is known about CD45 regulation in ectothermic vertebrates, this study examines the regulation of catfish CD45 mRNA isoform expression in clonal T and B cells in response to stimulation. Results show that mitogenic stimulation using catfish serum or concanavalin A induced expression of mRNAs for small CD45 isoforms, and isoform message expression was growth curve dependent, i.e. cells in logarithmic phase express message for smaller CD45 isoforms, whereas stationary phase cells express message for longer CD45 isoforms. In addition, cells treated with the protein synthesis inhibitor cycloheximide expressed message for longer CD45 isoforms, and treatment with lactacystin, which blocks protein degradation, rescued smaller isoform message expression. Collectively these data suggested that expression of CD45 isoforms, in catfish, at least at the mRNA level, is “constitutively dynamic” and highly dependent on extracellular stimuli.
Underexpression and overexpression of Fas and Fas ligand: a double-edged sword
2010, Annals of Allergy, Asthma and Immunology
Citation Excerpt :
A complete blood cell count may reveal anemia, thrombocytopenia, neutropenia, or lymphocytosis. In certain patients with ALPS, especially type Ia, DNT cells may show an increased expression of B-cell–specific CD45R isoform B220, which may improve the specificity of the flow screening assay for abnormal DNT cells.34–36 First-line therapy for ALPS includes systemic, high-dose corticosteroids.
To compare autoimmune lymphoproliferative syndrome (ALPS) and Stevens-Johnson syndrome (SJS) with respect to the defects in Fas- and Fas ligand (FasL)–mediated apoptosis.
Selected reviews, case reports, and original studies were searched in PubMed and MEDLINE for the keywords ALPS, SJS, Fas, FasL, and apoptosis.
Case reports of ALPS and SJS were selected as examples of Fas- and FasL-mediated diseases. In addition, we selected articles that examined the pathophysiology of apoptosis in the context of Fas-FasL interaction.
Failure to initiate apoptosis of abnormal T lymphocytes occurs in such diseases as ALPS, leading to the accumulation of double negative T cells with an increase in autoimmunity. In contrast to apoptotic failure, SJS is associated with a pathological increase in programmed keratinocyte cell death.
The consequences of dysregulated Fas- and FasL-mediated apoptosis leads to self-reactivity, malignant transformation, and immune dysfunction. An understanding of underlying mechanisms and qualitative assessment of Fas and FasL may have clinical benefits when control of these homeostatic mechanisms is in question.
Phenotypic and functional heterogeneity of human memory B cells
2008, Seminars in Immunology
Citation Excerpt :
Understanding the significance of these findings will require to first elucidate the relationship between the expression of B220 and: (1) the different pathways of memory cell development (GC-dependent and -independent); (2) different memory responses (T-dependent and -independent); (3) the division of labor between B220− and B220+ memory cells in terms of their effector functions (both antibody-dependent and -independent) and their relative participation in protective versus autoimmune responses [12]. One particularly intriguing possibility is that B220 expression could be lost during differentiation into resting (long-lived) central memory cells and upregulated during activation and generation of (short-lived) effector memory B cells [32,52–54]. This model would be consistent with the upregulation of B220 observed in activated mouse and human T cells before they undergo apoptosis [54–56].
Memory B cells are more heterogeneous than previously thought. Given that B cells play powerful antibody-independent effector functions, it seems reasonable to assume division of labor between distinct memory B cells subpopulations in both protective and pathogenic immune responses. Here we review the information emerging regarding the heterogeneity of human memory B cells. A better understanding of this topic should greatly improve our ability to target specific B cell subsets either in vaccine responses or in autoimmune diseases and organ rejection among other pathological conditions where B cells play central pathogenic roles.
Sorting out the causes of ALPS
2005, Journal of Pediatrics
The CD45 isoform B220 identifies select subsets of human B cells and B-cell lymphoproliferative disorders
2005, Human Pathology
The B220 isoform of CD45, a pan B-cell marker in mice, is expressed by only a subset of human B cells that do not express the memory B-cell marker CD27, suggesting that it is a differentiation-specific isoform of CD45. We examined normal human peripheral blood B cells, secondary lymphoid tissue, and a range of human B-cell lymphoproliferative disorders for the expression of B220 by flow cytometric immunophenotyping and immunohistochemical staining. We found that a subset of human B cells in peripheral blood is positive for B220 by flow cytometric immunophenotypic analysis. In reactive lymphoid tissues, B220 is expressed by B cells occupying the mantle zones and by a subpopulation of germinal center cells, but, in contrast, marginal zone B cells in the spleen do not express B220. Of 94 cases of B-cell lymphoproliferative disorders, 33 (35%) were positive for B220 by flow cytometric immunophenotypic analysis, including most cases of marginal zone lymphoma, follicular lymphoma, and lymphoplasmacytic lymphoma. In contrast, all cases of precursor B lymphoblastic leukemia/lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma were negative for B220. Immunohistochemical staining for B220 correlated with flow cytometric analysis for all cases studied by both methods. Our data demonstrate that B220 is expressed in a select subset of normal, reactive B cells in a pattern that is consistent with a marker of naive B cells. However, this restricted expression pattern is not seen in B-cell lymphoproliferative disorders. Discordance between the B220 expression patterns of normal mantle and marginal zone B cells and their respective neoplastic counterparts may aid in the distinction between normal and neoplastic proliferations at these anatomical sites.

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¹: J.J.H.B. and M.R.M. contributed equally to this work.

²: Current address and to whom correspondence should be addressed: Arkansas Children's Hospital Research Institute, 1120 Marshall Street, Slot 512-13, Little Rock, AR 72202. Fax: (501) 320-3173. E-mail: [email protected].

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Regular ArticleHuman T Cell Activation Induces the Expression of a Novel CD45 Isoform That Is Analogous to Murine B220 and Is Associated with Altered O-Glycan Synthesis and Onset of Apoptosis

Abstract

Cell

Cell

Pediatr. Clin. North Am.

Clin. Immunol.

Methods Enzymol.

Biochim. Biophys. Acta

Immunity

J. Biol. Chem.

Mol. Immunol.

J. Biol. Chem.

Immunity

J. Biol. Chem.

Mature T lymphocyte apoptosis—Immune regulation in a dynamic and unpredictable antigenic environment

Annu. Rev. Immunol.

Models of T cell anergy: Is there a common molecular pathway

J. Exp. Med.

Programmed cell death and extrathymic reduction of Vβ8+ CD4+ T cells in mice tolerant to staphylococcus aureus enterotoxin B

Nature

Superantigens: The paradox of T-cell activation versus inactivation

Int. Arch. Allergy Immunol.

Peripheral T cells undergoing superantigen-induced apoptosis in vivo express B220 and upregulate Fas and Fas ligand

J. Exp. Med.

Superantigen-driven peripheral deletion of T cells: Apoptosis occurs in cells that have lost the α/β T cell receptor

J. Immunol.

Activation signal induces the expression of B cell-specific CD45R epitope (6B2) on murine T cells

Scand. J. Immunol.

Expression of B220 on activated T cell blasts precedes apoptosis

Eur. J. Immunol.

Regular Article
Human T Cell Activation Induces the Expression of a Novel CD45 Isoform That Is Analogous to Murine B220 and Is Associated with Altered O-Glycan Synthesis and Onset of Apoptosis

Programmed cell death and extrathymic reduction of Vβ8⁺ CD4⁺ T cells in mice tolerant to staphylococcus aureus enterotoxin B