Lineage Switch Macrophages Can Present Antigen

Bretz, James D.; Chen, Shu-Chih; Redenius, Diane; Chang, Hsun-Lang; Esselman, Walter J.; Schwartz, Richard C.

doi:10.1155/1992/34586

Cited by 11 publications

(4 citation statements)

References 34 publications

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“…In a recent article, McClellan and colleagues reported that when incubated in vitro , blasts from some precursor B-cell acute lymphoblastic leukemia cells could apparently be functionally reprogrammed into myeloid lineage-mimicking cells that morphologically resemble and can, in some cases, function similarly to normal MPs ( 111 ). Several other studies had similar findings, demonstrating that malignant B-lymphoid cells can be reprogrammed to become MPs with apparently lymphoid and myeloid characteristics under certain conditions ( 112 – 115 ). Interestingly, we observed a similar phenomenon in MCL cases, as in vitro culture of primary MCL cells led to the presence of MPs after several days ( 70 ).…”

Section: Origin Of Tams In B-cell Lymphomasmentioning

confidence: 54%

The Role of Macrophage/B-Cell Interactions in the Pathophysiology of B-Cell Lymphomas

2018

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Macrophages (MPs) are heterogeneous, multifunctional, myeloid-derived leukocytes that are part of the innate immune system, playing wide-ranging critical roles in basic biological activities, including maintenance of tissue homeostasis involving clearance of microbial pathogens. Tumor-associated MPs (TAMs) are MPs with defined specific M2 phenotypes now known to play central roles in the pathophysiology of a wide spectrum of malignant neoplasms. Also, TAMs are often intrinsic cellular components of the essential tumor microenvironment (TME). In concert with lymphoid-lineage B and T cells at various developmental stages, TAMs can mediate enhanced tumor progression, often leading to poor clinical prognosis, at least partly through secretion of chemokines, cytokines, and various active proteases shown to stimulate tumor growth, angiogenesis, metastasis, and immunosuppression. Researchers recently showed that TAMs express certain key checkpoint-associated proteins [e.g., programmed cell death protein 1 (PD-1), programmed cell death-ligand 1 (PD-L1)] that appear to be involved in T-cell activation and that these proteins are targets of other specific checkpoint-blocking immunotherapies (anti-PD-1/PD-L1) currently part of new therapeutic paradigms for chemotherapy-resistant neoplasms. Although much is known about the wide spectrum and flexibility of MPs under many normal and neoplastic conditions, relatively little is known about the increasingly important interactions between MPs and B-lymphoid cells, particularly in the TME in patients with aggressive B-cell non-Hodgkin lymphoma (NHL-B). Normal and neoplastic lymphoid and myeloid cell/MP lineages appear to share many primitive cellular characteristics as well as transcriptional factor interactions in human and animal ontogenic studies. Such cells are capable of ectopic transcription factor-induced lineage reprogramming or transdifferentiation from early myeloid/monocytic lineages to later induce B-cell lymphomagenesis in experimental in vivo murine systems. Close cellular interactions between endogenous clonal neoplastic B cells and related aberrant myeloid precursor cells/MPs appear to be important interactive components of aggressive NHL-B that we discuss herein in the larger context of the putative role of B-cell/MP cellular lineage interactions involved in NHL-B pathophysiology during ensuing lymphoma development.

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Section: Origin Of Tams In B-cell Lymphomasmentioning

confidence: 54%

The Role of Macrophage/B-Cell Interactions in the Pathophysiology of B-Cell Lymphomas

2018

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“…CD45 is a transmembrane PTP of hematopoietic cells composed of 1268 total amino acids with an external domain containing alternately used exons, which leads to the lymphocyte-specific expression of at least eight different isoforms (1,5,6). The cytoplasmic domain consists of 702 amino acids and contains two tandem repeated PTP domains designated D1 and D2 (1).…”

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confidence: 99%

Phosphorylation of CD45 by Casein Kinase 2

Wang

Guo

Liang

et al. 1999

Journal of Biological Chemistry

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CD45 is a receptor-type protein-tyrosine phosphatase (PTP) that is required for antigen-specific stimulation and proliferation in lymphocytes. This study was designed to determine the nature of specific kinases in lymphocytes that phosphorylate CD45 and to determine the effect of phosphorylation on CD45 PTP activity. A major cytoplasmic lymphocyte kinase that phosphorylated CD45 was identified as casein kinase 2 (CK2) by use of an in-gel kinase assay in combination with immunoprecipitation, immunodepletion, and specific inhibition. Mutational analysis of CK2 consensus sites showed that the target for CK2 was in an acidic insert of 19 amino acids in the D2 domain, and Ser to Ala mutations at amino acids 965, 968, 969, and 973 abrogated CK2 phosphorylation of CD45. CK2 phosphorylation increased CD45 activity 3-fold toward phosphorylated myelin basic protein, and this increase was reversible by PP2A treatment. Mutation of Ser to Glu at the CK2 sites had the same effect as phosphorylation and also tripled the V max of CD45. CD45 isolated in vivo was highly phosphorylated and could not be phosphorylated by CK2 without prior dephosphorylation with phosphatase PP2A. We conclude that CK2 is a major lymphocyte kinase that is responsible for in vivo phosphorylation of CD45, and phosphorylation at specific CK2 sites regulates CD45 PTP activity.The role of CD45 protein-tyrosine phosphatase (PTP) 1 in lymphocyte signaling has been the subject of extensive investigation (1-4). CD45 is a transmembrane PTP of hematopoietic cells composed of 1268 total amino acids with an external domain containing alternately used exons, which leads to the lymphocyte-specific expression of at least eight different isoforms (1, 5, 6). The cytoplasmic domain consists of 702 amino acids and contains two tandem repeated PTP domains designated D1 and D2 (1). The membrane-proximal PTP domain (D1) is constitutively active, and the second PTP domain (D2) is considered to be inactive (7). The catalytic activity of the D1 but not the D2 domain is required for TCR signal transduction in CD45-deficient cell lines (8). The role of CD45 in the antigenspecific activation of B and T cells has been documented by demonstrating that T cells and B cells lacking CD45 fail to respond to antigen stimulation (9, 10). This observation has been confirmed in CD45 knockout mice in which the antigen signaling capacity of T and B cells was severely diminished and the transition of thymocytes to maturity was impaired (11,12). CD45 is believed to activate the Src family protein-tyrosine kinases by dephosphorylating the regulatory Tyr(P) near the C terminus of T cell receptor or B cell receptor-associated Src family kinases (13-16). However, recently it has become clear that the regulation of Src family kinases is likely to be more complex since the discovery that the activating tyrosine phosphorylation site in the kinase domain is also dephosphorylated by CD45 (17). The importance of the CD45 PTP activity in the activation of T cells has been demonstrated by showing that chim...

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“…Total cellular RNA was analyzed by RT-PCR as previously described (26). Basically, 0.5 to 1.0 pg of RNA was reverse transcribed into cDNA using a 3' antisense oligonucleotide primer specific for murine CD45 exon 9 described by Bretz et al (26).…”

Section: Molecular Analysesmentioning

confidence: 99%

“…Basically, 0.5 to 1.0 pg of RNA was reverse transcribed into cDNA using a 3' antisense oligonucleotide primer specific for murine CD45 exon 9 described by Bretz et al (26). One-half of the cDNA samples were amplified for 35 cycles in a 50 pl PCR reaction mixture containing 500 pM dNTPs and 400 ng of the 5' (specific to exon 2) and 3' oligonucleotides according to the conditions described previously (26). Reaction products were analyzed on 2% NuSieve gel stained with ethidium bromide.…”

Section: Molecular Analysesmentioning

confidence: 99%

Bone Marrow Stroma-Dependent Modulation of CD45R Isoform Expression on Abelson Virus Transformed Pre-B Cells

Fizzotti

Clark

1995

Immunological Investigations

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The CD45 glycoprotein family exhibits cell-lineage-associated structural heterogeneity which is due, in part, to alternative pre-mRNA splicing. The Abelson murine leukemia (A-MuLV) preferentially transforms immature B cells that express a B-cell-specific high molecular weight CD45 isoform, called B220. However, we observed that A-MuLV-transformed cell lines are often B220- while maintaining high levels of "pan" CD45 expression. In vitro transformation of murine bone marrow revealed that the stromal microenvironment over which A-MuLV-transformed lymphoblasts are grown affected the B220 phenotype of the pre-B cells. Over a period of a few weeks, B220+ populations grown over a clonal stromal cell line gradually became B220-. However, the transition from a B220+ to B220- phenotype was dependent on the lot of fetal calf serum used. In contrast, cells grown over a heterogeneous bone marrow stroma maintained B220+ expression for long periods of time. The appearance of B220- cells in clonal B220+ populations indicated that the change in phenotype resulted in part from modulation of B220 expression. B220- B-cell lines did not express the high molecular weight CD45 RNA species indicating that the B220- phenotype was due to alternative pre-mRNA splicing. Finally, the shift from B220+ to B220- was not accompanied by changes in the stage of development of the cultures. These observations demonstrate that expression of B220 is not required for the continued proliferation of Abelson-transformed pre-B cells and is regulated by unknown environmental factors.

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Lineage Switch Macrophages Can Present Antigen

Cited by 11 publications

References 34 publications

The Role of Macrophage/B-Cell Interactions in the Pathophysiology of B-Cell Lymphomas

The Role of Macrophage/B-Cell Interactions in the Pathophysiology of B-Cell Lymphomas

Phosphorylation of CD45 by Casein Kinase 2

Bone Marrow Stroma-Dependent Modulation of CD45R Isoform Expression on Abelson Virus Transformed Pre-B Cells

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