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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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Western blot analysis of SHP-1 in lysates from the  Burkitt lymphomas, Ramos,  Daudi and WW2BL, the LCLs,  WW2LCL and JY, and the B  lymphoma BJAB. The numbers  at the bottom of the gel represent the concentration of SHP-1  in the cellular lysates as determined by ELISA.
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Figure 1: Western blot analysis of SHP-1 in lysates from the Burkitt lymphomas, Ramos, Daudi and WW2BL, the LCLs, WW2LCL and JY, and the B lymphoma BJAB. The numbers at the bottom of the gel represent the concentration of SHP-1 in the cellular lysates as determined by ELISA.

Mentions: We initially compared the amount of SHP-1 in six human B cell lines by Western blot analysis and found that the PTPase was expressed at different levels among these lines (Fig. 1). Although SHP-1 was easily detected in lysates from two EBV-immortalized lymphoblastoid cell lines (LCLs), WW2LCL and JY, it was reduced in three of three Burkitt lymphomas: Ramos, Daudi, and WW2BL. BJAB, a B lymphoma line morphologically resembling EBV-negative Burkitt lymphoma but lacking the characteristic chromosomal translocation that involves c-myc (41), expressed higher levels of SHP-1. To quantitatively assay SHP-1 concentration in cell lysates, we developed an ELISA using an affinity-purified polyclonal rabbit antibody specific for SHP-1 as both the capture and detecting antibody, and recombinant SHP-1 as the standard. The measurement of SHP-1 confirmed the results of the semiquantitative Western blots, indicating that in the three Burkitt lymphomas with c-myc translocations, the SHP-1 intracellular concentrations were reduced relative to the levels in the EBV-immortalized lines (Fig. 1).


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)

Western blot analysis of SHP-1 in lysates from the  Burkitt lymphomas, Ramos,  Daudi and WW2BL, the LCLs,  WW2LCL and JY, and the B  lymphoma BJAB. The numbers  at the bottom of the gel represent the concentration of SHP-1  in the cellular lysates as determined by ELISA.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Western blot analysis of SHP-1 in lysates from the Burkitt lymphomas, Ramos, Daudi and WW2BL, the LCLs, WW2LCL and JY, and the B lymphoma BJAB. The numbers at the bottom of the gel represent the concentration of SHP-1 in the cellular lysates as determined by ELISA.
Mentions: We initially compared the amount of SHP-1 in six human B cell lines by Western blot analysis and found that the PTPase was expressed at different levels among these lines (Fig. 1). Although SHP-1 was easily detected in lysates from two EBV-immortalized lymphoblastoid cell lines (LCLs), WW2LCL and JY, it was reduced in three of three Burkitt lymphomas: Ramos, Daudi, and WW2BL. BJAB, a B lymphoma line morphologically resembling EBV-negative Burkitt lymphoma but lacking the characteristic chromosomal translocation that involves c-myc (41), expressed higher levels of SHP-1. To quantitatively assay SHP-1 concentration in cell lysates, we developed an ELISA using an affinity-purified polyclonal rabbit antibody specific for SHP-1 as both the capture and detecting antibody, and recombinant SHP-1 as the standard. The measurement of SHP-1 confirmed the results of the semiquantitative Western blots, indicating that in the three Burkitt lymphomas with c-myc translocations, the SHP-1 intracellular concentrations were reduced relative to the levels in the EBV-immortalized lines (Fig. 1).

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