1: Stem Cells Dev. 2006 Feb;15(1):1-3.


Comment in:
Stem Cells Dev. 2006 Dec;15(6):753.

The continuum of stem cell transdifferentiation: possibility of hematopoietic stem cell plasticity with concurrent CD45 expression.

Udani VM.

Stanford University School of Medicine, Palo Alto, CA 94305, USA. vikudani@stanford.edu

Recent years have seen a surge of scientific research examining adult stem cell plasticity. For example, the hematopoietic stem cell has been shown to give rise to skin, respiratory epithelium, intestinal epithelium, renal epithelium, liver parenchyma, pancreas, skeletal muscle, vascular endothelium, myocardium, and central nervous system (CNS) neurons. The potential for such stem cell plasticity seems to be enhanced by stressors such as injury and neoplasia. Interestingly, recent studies have demonstrated that hematopoietic stem cells may be able to adopt certain nonhematopoietic phenotypes, such as endothelial, neural, or skeletal muscle phenotypes, without entirely losing their initial hematopoietic identity. We propose that transdifferentiation can, in certain conditions, be a partial rather than a complete event, and we encourage further investigation into the phenomenon of a stem cell simultaneously expressing phenotypic features of two distinct cell fates.

Publication Types:
Review

PMID: 16522157 [PubMed - indexed for MEDLINE]

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2: Trends Immunol. 2006 Mar;27(3):146-53. Epub 2006 Jan 18.


Altered CD45 expression and disease.

Tchilian EZ, Beverley PC.

The Edward Jenner Institute for Vaccine Research, Compton, Berkshire, UK RG 20 7NN. elma.tchilian@jenner.ac.uk

CD45, the leucocyte common antigen, is a haemopoietic cell-specific tyrosine phosphatase. Many isoforms are generated by alternative splicing, but their function remains obscure. The extracellular domain of CD45 is highly polymorphic in all vertebrates. Importantly, human polymorphic variants that alter CD45 isoform expression are associated with autoimmune and infectious diseases, establishing CD45 as an important immunomodulator with a significant influence on disease burden. Here, we discuss the new opportunities provided by the human variants for investigating and understanding how CD45 regulates antigen receptor signalling, cytokine responses and apoptosis.

Publication Types:
Review

PMID: 16423560 [PubMed - indexed for MEDLINE]

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3: Leuk Lymphoma. 2000 Sep;39(1-2):51-5.


Proliferation of immature myeloma cells by interleukin-6 is associated with CD45 expression in human multiple myeloma.

Ishikawa H, Mahmoud MS, Fujii R, Abroun S, Kawano MM.

Department of Immunohematology, Yamaguchi University School of Medicine, Ube, Japan. hishika@po.cc.yamaguchi-u.ac.jp

Multiple myeloma (MM) is a hematologic malignancy of human plasma cells, and myeloma cells can be classified into several subpopulations according to phenotypic differences, such as CD38 MPC-1- CD49e- immature, CD38 MPC-1+ CD49e- intermediate and CD38 MPC-1+ CD49e+ mature myeloma cells. The expression of the CD45 molecule on myeloma cells is quite variable, and the physiological consequence of CD45 on myeloma cells is still unknown. Recently, we have found that a few MPC-1- immature myeloma cells express CD45 antigens while most myeloma cells do not express the CD45. MPC-1- CD45+ CD49e- but not MPC-1- CD45- CD49e- immature cells contain proliferating cells in response to interleukin-6 (IL-6). IL-6 can also induce expression of CD45 on the MPC-1- CD45- subpopulation of immature myeloma cells. In addition, myeloma cell lines responding to IL-6 express CD45, whereas cell lines proliferating independent of IL-6 do not express CD45. In the U266 cell line, IL-6 leads to the induction of CD45 expression and cell proliferation, indicating that IL-6-induced effects are closely linked to CD45 expression. Thus, there is a heterogeneity in human myeloma cells, and among these subpopulations immature myeloma cells expressing the CD45 molecules appear to proliferate in response to IL-6. In this review we propose the involvement of CD45 in MM pathogenesis, and the possible implications of CD45 as both a phenotypic marker and a functional molecule is discussed.

Publication Types:
Review

PMID: 10975383 [PubMed - indexed for MEDLINE]

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4: Leuk Lymphoma. 1996 Jan;20(3-4):217-22.


CD45 (leucocyte common antigen) expression in T and B lymphocyte subsets.

Poppema S, Lai R, Visser L, Yan XJ.

Department of Laboratory Medicine, Cross Cancer Institute, Alberta, Canada.

CD45 is the dominant tyrosine phosphatase in haematopoietic cells and can modulate the effects of many other signaling molecules by dephosphorylation. The extracellular portion of CD45 has considerable variability due to differential splicing and glycosylation. This may allow for interactions with a variety of ligands expressed on interacting cells or on the same cell surface. Monoclonal anti CD45 antibodies that are reactive with epitopes that result from differential splicing and glycosylation can distinguish between cell populations that differ in maturation and function. These reagents can be used in the immunophenotyping of hematopoietic malignancies as well as in immunodeficiencies and autoimmune diseases. Several studies have shown that different anti CD45 reagents have different activating or inhibiting effects in vitro on a variety of T and B cell activation events. There are some indications that anti CD45 reagents can also selectively modify lymphocyte function in vivo. Such applications could potentially allow for the selective upregulation and down regulation of lymphocyte functions in a variety of immunologically mediated diseases.

Publication Types:
Review

PMID: 8624459 [PubMed - indexed for MEDLINE]

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5: Immunol Cell Biol. 1993 Feb;71 ( Pt 1):59-69.


Adhesive interactions in thymic development: does selective expression of CD45 isoforms promote stage-specific microclustering in the assembly of functional adhesive complexes on differentiating T lineage lymphocytes?

Pilarski LM.

Department of Immunology, University of Alberta, Edmonton, Canada.

CD45 isoform transitions appear to play essential roles in both life and death, and correlate with the stages of thymocyte development during which there is a change in physical location from medullary and/or outer cortical areas to the inner cortex. This work speculates that CD45 isoforms, through a focal role in the assembly of adhesive complexes mediated by the external domains, participate in the maintenance and/or modulation of migratory behaviour by differentiating thymocytes, or alternatively in the anchoring of thymocytes in a generative micro-environment. The objective of the sections that follow is to formulate the hypothesis that CD45 isoforms, through their differential interactions with adhesion molecules expressed by T cells, profoundly influence cell motility and consequent micro-environmental localization. An adhesive assembly of CD45 and adhesion molecules on the outside, and of the adhesive complex with the cytoskeleton on the inside, would promote CD45-mediated regulation of adhesion/de-adhesion through lateral external interactions mediated by external domains of CD45 isoforms, through enzymatic modulation of the cytoplasmic domains of adhesion molecules by the CD45 tyrosine phosphatase activity, and through phosphatase control of cytoskeletal assembly and disassembly.

Publication Types:
Review

PMID: 8436412 [PubMed - indexed for MEDLINE]

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6: Hematol Oncol Clin North Am. 1992 Apr;6(2):297-322.


Monoclonal circulating B cells in multiple myeloma. A continuously differentiating, possibly invasive, population as defined by expression of CD45 isoforms and adhesion molecules.

Pilarski LM, Jensen GS.

Department of Immunology, University of Alberta, Edmonton, Canada.

The origin of the malignant stem cell in multiple myeloma, despite years of investigation by many laboratories, remains elusive. We have described a population of monoclonal circulating B-lineage lymphocytes that has been detected in all myeloma patients analyzed, both at diagnosis and after chemotherapy, and that has many properties consistent with its definition as either a stem cell compartment or an intermediate between the stem cell and the bone marrow localized plasma cells. On average, 40% to 50% of peripheral blood mononuclear cells are abnormal B cells that express CD10 and PCA-1 in conjunction with B-lineage markers CD19, CD20, and CD24 and variable expression of CD5. The B cells are monoclonal by Southern blot analysis and represent a highly pleiomorphic population. The migratory patterns of these cells are unknown, and their presence in blood may reflect cells in transit from a parent organ such as spleen to bone marrow for terminal differentiation, or they may originate in the bone marrow prior to circulation and seeding of other skeletal or extraskeletal sites. The working hypothesis underlying this work postulates that these abnormal B cells originate outside the marrow, giving rise to plasma cells only after migration to the bone marrow, which provides a microenvironment conducive to terminal plasma cell differentiation. Bone marrow plasma cells do not include an actively proliferating component and are terminally differentiated end stage cells. In contrast, the circulating abnormal B cells include proliferating cells and appear to be heterogeneous in differentiation stage. Analysis of CD45 isoform expression indicates a population continuously differentiating from a late B-cell stage through the early plasma cell stages to an end stage plasma cell. Quantitative and qualitative expression of CD45 has been shown to characterize B-cell development, with a high density of the CD45RA isoform on mature resting B cells, a transition to CD45R0 on activated B cells, and a gradual loss of total CD45, predominantly of the CD45R0 isoform, during plasma cell development until, on end stage plasma cells, all CD45 expression is lost. In myeloma patients, all of these B-cell stages are represented, with the least differentiated B cells occurring in blood, intermediate stages in both blood and marrow, the most differentiated B and/or plasma cells in the bone marrow.(ABSTRACT TRUNCATED AT 400 WORDS)

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 1533857 [PubMed - indexed for MEDLINE]

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7: Semin Immunol. 1992 Feb;4(1):35-41.


Functional analysis of human T cell subsets defined by CD45 isoform expression.

Beverley PC.

Imperial Cancer Research Fund Human Tumour Immunology Group, University College and Middlesex School of Medicine, London, UK.

The properties of human CD45RA and CD45RO T cells are described. CD45RO cells respond to recall antigens and provide help for B lymphocytes. They produce a wide variety of cytokines including IL-2, IL-4 and IFN-gamma. CD45RA T cells respond poorly to recall antigens and produce mainly IL-2. The phenotype of CD45RO cells suggests that they may be in cycle and in vivo data shows that they have a short lifespan while CD45RA cells are long-lived. The lineage relationship of the two subsets is not clear but in vivo and in vitro evidence suggests bi-directional conversion between CD45RA and CD45RO phenotypes.

Publication Types:
Review

PMID: 1534262 [PubMed - indexed for MEDLINE]

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8: Biochem Soc Trans. 1992 Feb;20(1):188-90.


Subsets of CD4+ T cells defined by their expression of different isoforms of the leucocyte-common antigen, CD45.

Mason D.

M.R.C. Cellular Immunology Unit, Sir William Dunn School of Pathology, Oxford, U.K.

Publication Types:
Review

PMID: 1386041 [PubMed - indexed for MEDLINE]

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9: Immunol Res. 1991;10(3-4):493-6.


Mucosal T cell subsets in coeliac disease: expression of T cell receptor and CD45 isoforms.

Halstensen TS, Brandtzaeg P.

Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), University of Oslo, National Hospital, Norway.

Publication Types:
Review

PMID: 1835492 [PubMed - indexed for MEDLINE]

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10: Immunol Res. 1991;10(3-4):196-8.


CD45 isoform expression: implications for recirculation of naive and memory cells.

Beverley PC.

Imperial Cancer Research Fund, University College and Middlesex School of Medicine, Courtauld Institute of Biochemistry, London, UK.

Publication Types:
Review

PMID: 1835477 [PubMed - indexed for MEDLINE]

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11: Curr Top Microbiol Immunol. 1990;159:79-96.


Subsets of rat CD4+ T cells defined by their differential expression of variants of the CD45 antigen: developmental relationships and in vitro and in vivo functions.

Powrie F, Mason D.

Medical Research Council Cellular Immunology Unit, Sir William Dunn School of Pathology, University of Oxford, United Kingdom.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 1971782 [PubMed - indexed for MEDLINE]

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12: Immunol Lett. 1989 Jun 1;21(3):187-98.


Selective expression of CD45 isoforms and of maturation antigens during human thymocyte differentiation: observations and hypothesis.

Pilarski LM, Deans JP.

Department of Immunology, University of Alberta, Edmonton, Canada.

Selective expression of high and low molecular weight isoforms of CD45 (T200) occurs coincident with activation of mature T lymphocytes. Expression of CD45 p180 and CDw29 defines antigen-experienced memory T cells in the periphery, and expression of CD45R (CD45 p205/220) defines naive T cells. Upon activation, CD45R+ T cells lose CD45R and acquire CD45 p180 and high density CDw29. In this review we discuss the expression of CD45 isoforms, CDw29, pgp-1 and CD1 on human thymocytes and develop the hypothesis that expression of CD45R marks the generative thymic lineage while expression of CD45 p180 marks those cells destined for intrathymic death. This hypothesis is supported by evidence from phenotypic, molecular and functional analysis of thymocyte subsets. We propose that expression of high molecular weight isoforms of CD45 is essential for growth and differentiation of immature T cells and that inappropriate rearrangement or specificity of TCR activates a transition from expression of CD45R to that of CD45 p180 and intrathymic death.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 2527812 [PubMed - indexed for MEDLINE]