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Downregulated expression of SHP-1 in Burkitt lymphomas and germinal center B lymphocytes.

Delibrias CC, Floettmann JE, Rowe M, Fearon DT - J. Exp. Med. (1997)

Bottom Line: SHP-1 is an SH2 domain-containing phosphotyrosine phosphatase that negatively regulates activation of B cells and other cells of hematopoietic lineages.In CD38-high B cells, SHP-1 concentration was 20% of that of mantle zone B cells from the same donor.Therefore, germinal center B cells may have a developmentally regulated, low threshold for cellular activation.

View Article: PubMed Central - PubMed

Affiliation: Wellcome Trust Immunology Unit, Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge CB2 2SP, United Kingdom.

ABSTRACT
We wish to identify developmental changes in germinal center B cells that may contribute to their rapid growth. SHP-1 is an SH2 domain-containing phosphotyrosine phosphatase that negatively regulates activation of B cells and other cells of hematopoietic lineages. We have found that in all 13 EBV-negative and 11 EBV-positive Burkitt lymphomas with a nonlymphoblastoid phenotype, the mean concentration of SHP-1 was reduced to 5% of that of normal B and T cells. The possibility that this diminished expression of SHP-1 was related to the germinal center phenotype of Burkitt lymphomas was supported by the low to absent immunofluorescent staining for SHP-1 in germinal centers, and by the inverse relationship between the concentration of SHP-1 and the expression of the germinal center marker CD38 on purified tonsillar B cells. In CD38-high B cells, SHP-1 concentration was 20% of that of mantle zone B cells from the same donor. This reduction in SHP-1 is comparable to that of cells from motheaten viable mev/mev mice in which there is dysregulated, spontaneous signaling by cytokine and antigen receptors. Therefore, germinal center B cells may have a developmentally regulated, low threshold for cellular activation.

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Concentration of  SHP-1 in primary and transformed human cells as determined by ELISA. The closed  symbols designate EBV-positive  Burkitt lymphomas. The shaded  area represents the mean ± 1 SD  of the SHP-1 levels in normal B  and T cells.
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Figure 2: Concentration of SHP-1 in primary and transformed human cells as determined by ELISA. The closed symbols designate EBV-positive Burkitt lymphomas. The shaded area represents the mean ± 1 SD of the SHP-1 levels in normal B and T cells.

Mentions: We assayed the concentration of SHP-1 in a large panel of cells, including primary T and B cells, granulocytes, EBV-immortalized LCLs from healthy individuals, EBV-negative and -positive Burkitt lymphomas, and LCLs established with normal B cells from patients with Burkitt lymphoma (Fig. 2). The concentration of SHP-1 in normal primary T and B cells purified from tonsils of five individuals ranged between 0.04 and 0.14% (mean = 0.085%) of total cellular protein (Fig. 2). Activation of B cells in vitro with pokeweed mitogen did not alter the levels of SHP-1 (data not shown). Granulocytes purified from the peripheral blood of five individuals had similar concentrations of SHP-1 (mean = 0.062% of total cellular protein), as did eight LCL lines from normal individuals (mean = 0.070% of total cellular protein). In 13 of 13 EBV-negative Burkitt lymphoma lines, SHP-1 levels were reduced by one to three orders of magnitude relative to the levels in normal lymphocytes (mean = 0.004% of total cellular protein). Group I/II EBV-positive Burkitt lines, which have retained the original tumor biopsy phenotype and which morphologically resemble EBV-negative lines, had comparably reduced concentrations of SHP-1 (mean = 0.005% of total cellular protein). In contrast, the levels of SHP-1 were normal in four of four group III EBV-positive Burkitt lymphomas (mean = 0.077% of total cellular protein) which resemble LCLs morphologically, by surface phenotype, and by EBV gene expression (42). In the seven Burkitt lines that had paired LCLs established from normal B cells of these individuals, the lymphomas had reduced levels of SHP-1 (mean = 0.003% of total cellular protein), whereas the LCLs (mean = 0.094% of total cellular protein) did not differ from normal B cells or from the cell lines established from healthy individuals.


Downregulated expression of SHP-1 in Burkitt lymphomas and germinal center B lymphocytes.

Delibrias CC, Floettmann JE, Rowe M, Fearon DT - J. Exp. Med. (1997)

Concentration of  SHP-1 in primary and transformed human cells as determined by ELISA. The closed  symbols designate EBV-positive  Burkitt lymphomas. The shaded  area represents the mean ± 1 SD  of the SHP-1 levels in normal B  and T cells.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199125&req=5

Figure 2: Concentration of SHP-1 in primary and transformed human cells as determined by ELISA. The closed symbols designate EBV-positive Burkitt lymphomas. The shaded area represents the mean ± 1 SD of the SHP-1 levels in normal B and T cells.
Mentions: We assayed the concentration of SHP-1 in a large panel of cells, including primary T and B cells, granulocytes, EBV-immortalized LCLs from healthy individuals, EBV-negative and -positive Burkitt lymphomas, and LCLs established with normal B cells from patients with Burkitt lymphoma (Fig. 2). The concentration of SHP-1 in normal primary T and B cells purified from tonsils of five individuals ranged between 0.04 and 0.14% (mean = 0.085%) of total cellular protein (Fig. 2). Activation of B cells in vitro with pokeweed mitogen did not alter the levels of SHP-1 (data not shown). Granulocytes purified from the peripheral blood of five individuals had similar concentrations of SHP-1 (mean = 0.062% of total cellular protein), as did eight LCL lines from normal individuals (mean = 0.070% of total cellular protein). In 13 of 13 EBV-negative Burkitt lymphoma lines, SHP-1 levels were reduced by one to three orders of magnitude relative to the levels in normal lymphocytes (mean = 0.004% of total cellular protein). Group I/II EBV-positive Burkitt lines, which have retained the original tumor biopsy phenotype and which morphologically resemble EBV-negative lines, had comparably reduced concentrations of SHP-1 (mean = 0.005% of total cellular protein). In contrast, the levels of SHP-1 were normal in four of four group III EBV-positive Burkitt lymphomas (mean = 0.077% of total cellular protein) which resemble LCLs morphologically, by surface phenotype, and by EBV gene expression (42). In the seven Burkitt lines that had paired LCLs established from normal B cells of these individuals, the lymphomas had reduced levels of SHP-1 (mean = 0.003% of total cellular protein), whereas the LCLs (mean = 0.094% of total cellular protein) did not differ from normal B cells or from the cell lines established from healthy individuals.

Bottom Line: SHP-1 is an SH2 domain-containing phosphotyrosine phosphatase that negatively regulates activation of B cells and other cells of hematopoietic lineages.In CD38-high B cells, SHP-1 concentration was 20% of that of mantle zone B cells from the same donor.Therefore, germinal center B cells may have a developmentally regulated, low threshold for cellular activation.

View Article: PubMed Central - PubMed

Affiliation: Wellcome Trust Immunology Unit, Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge CB2 2SP, United Kingdom.

ABSTRACT
We wish to identify developmental changes in germinal center B cells that may contribute to their rapid growth. SHP-1 is an SH2 domain-containing phosphotyrosine phosphatase that negatively regulates activation of B cells and other cells of hematopoietic lineages. We have found that in all 13 EBV-negative and 11 EBV-positive Burkitt lymphomas with a nonlymphoblastoid phenotype, the mean concentration of SHP-1 was reduced to 5% of that of normal B and T cells. The possibility that this diminished expression of SHP-1 was related to the germinal center phenotype of Burkitt lymphomas was supported by the low to absent immunofluorescent staining for SHP-1 in germinal centers, and by the inverse relationship between the concentration of SHP-1 and the expression of the germinal center marker CD38 on purified tonsillar B cells. In CD38-high B cells, SHP-1 concentration was 20% of that of mantle zone B cells from the same donor. This reduction in SHP-1 is comparable to that of cells from motheaten viable mev/mev mice in which there is dysregulated, spontaneous signaling by cytokine and antigen receptors. Therefore, germinal center B cells may have a developmentally regulated, low threshold for cellular activation.

Show MeSH
Related in: MedlinePlus