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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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Kinetics of upregulation of SHP-1 expression in  untreated Burkitt lymphomas  (open squares), in lymphomas  stimulated with 20 ng/ml PMA  (closed squares), or with 5 μg/ml  polyclonal goat F(ab′)2 anti-IgM  (closed circles). † >70% of WW2BL  cells had undergone apoptosis after 72 h of PMA treatment.
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Figure 3: Kinetics of upregulation of SHP-1 expression in untreated Burkitt lymphomas (open squares), in lymphomas stimulated with 20 ng/ml PMA (closed squares), or with 5 μg/ml polyclonal goat F(ab′)2 anti-IgM (closed circles). † >70% of WW2BL cells had undergone apoptosis after 72 h of PMA treatment.

Mentions: The apparent reversion to normal of SHP-1 levels in EBV-infected Burkitt lymphomas in association with an LCL phenotype suggested that the expression of the PTPase could be modulated. This possibility was demonstrated by stimulating the EBV-negative Burkitt line, Ramos, and the EBV-positive lines Daudi and WW2BL, with either phorbol ester (PMA) or polyclonal antibody to IgM. In Ramos and Daudi, both treatments caused time-dependent increases of 10–50-fold in the cellular concentration of SHP-1, whereas in the WW2BL line, only PMA was effective because these cells do not express mIg (Fig. 3). Additional experiments with the Ramos line showed that the surface markers characteristic of Burkitt lymphomas, CD38 and CD77, were unchanged after mIgM ligation, but that the ratio of CD19 to CD22 was inverted due to an increase in CD22 and a decrease in cell surface CD19 (data not shown). As previously reported (43), stimulation of all three Burkitt lymphomas caused apoptosis (not shown).


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)

Kinetics of upregulation of SHP-1 expression in  untreated Burkitt lymphomas  (open squares), in lymphomas  stimulated with 20 ng/ml PMA  (closed squares), or with 5 μg/ml  polyclonal goat F(ab′)2 anti-IgM  (closed circles). † >70% of WW2BL  cells had undergone apoptosis after 72 h of PMA treatment.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Kinetics of upregulation of SHP-1 expression in untreated Burkitt lymphomas (open squares), in lymphomas stimulated with 20 ng/ml PMA (closed squares), or with 5 μg/ml polyclonal goat F(ab′)2 anti-IgM (closed circles). † >70% of WW2BL cells had undergone apoptosis after 72 h of PMA treatment.
Mentions: The apparent reversion to normal of SHP-1 levels in EBV-infected Burkitt lymphomas in association with an LCL phenotype suggested that the expression of the PTPase could be modulated. This possibility was demonstrated by stimulating the EBV-negative Burkitt line, Ramos, and the EBV-positive lines Daudi and WW2BL, with either phorbol ester (PMA) or polyclonal antibody to IgM. In Ramos and Daudi, both treatments caused time-dependent increases of 10–50-fold in the cellular concentration of SHP-1, whereas in the WW2BL line, only PMA was effective because these cells do not express mIg (Fig. 3). Additional experiments with the Ramos line showed that the surface markers characteristic of Burkitt lymphomas, CD38 and CD77, were unchanged after mIgM ligation, but that the ratio of CD19 to CD22 was inverted due to an increase in CD22 and a decrease in cell surface CD19 (data not shown). As previously reported (43), stimulation of all three Burkitt lymphomas caused apoptosis (not shown).

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