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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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Inverse correlation between the levels of SHP-1 and CD38  expression in GC B cells. (A) CD19-positive, CD38-negative B cells  (R2) were purified by sorting from high density tonsillar B cells (top).  CD38-high (R3) and CD38-low (R4) B cells were purified by sorting  from low density, CD39-negative tonsillar B cells (bottom). (B) The expression of SHP-1 and CD38 in the R2, R3, and R4 subpopulations of  sorted tonsillar B cells was determined by ELISA and flow cytometry, respectively.
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Figure 6: Inverse correlation between the levels of SHP-1 and CD38 expression in GC B cells. (A) CD19-positive, CD38-negative B cells (R2) were purified by sorting from high density tonsillar B cells (top). CD38-high (R3) and CD38-low (R4) B cells were purified by sorting from low density, CD39-negative tonsillar B cells (bottom). (B) The expression of SHP-1 and CD38 in the R2, R3, and R4 subpopulations of sorted tonsillar B cells was determined by ELISA and flow cytometry, respectively.

Mentions: We also quantitated SHP-1 expression by ELISA in purified GC B cells. Total CD38- and CD19-positive B cells that had been purified from five tonsils had SHP-1 concentration that ranged from 31 to 36% (mean 33%) of the concentration in CD38-negative, CD19-positive cells. GC B cells appeared to vary according to the intensity with which they stained for CD38 (Fig. 5). Therefore, we sorted GC B cells into CD38-high and -low populations, and compared their levels of SHP-1 to the levels in CD38-negative B cells. There was an inverse relationship between CD38 expression and SHP-1 content, with the highest CD38 expressing cells having a SHP-1 level that was only 20% that of CD38-negative cells (Fig. 6). CD38-positive B cells were also sorted on the basis of CD77 expression and assayed for SHP-1; CD77-positive and -negative GC B cells had identical and diminished levels of SHP-1, indicating that both centroblasts and centrocytes downregulate the PTPase (data not shown). In two of two experiments, CD38-negative, IgG-positive, CD19-positive B cells had the same concentration of SHP-1 as did resting, CD38-negative, CD19-positive B cells purified from the same donors (data not shown), suggesting that SHP-1 levels return to normal when GC cells differentiate into memory B cells.


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)

Inverse correlation between the levels of SHP-1 and CD38  expression in GC B cells. (A) CD19-positive, CD38-negative B cells  (R2) were purified by sorting from high density tonsillar B cells (top).  CD38-high (R3) and CD38-low (R4) B cells were purified by sorting  from low density, CD39-negative tonsillar B cells (bottom). (B) The expression of SHP-1 and CD38 in the R2, R3, and R4 subpopulations of  sorted tonsillar B cells was determined by ELISA and flow cytometry, respectively.
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Related In: Results  -  Collection

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Figure 6: Inverse correlation between the levels of SHP-1 and CD38 expression in GC B cells. (A) CD19-positive, CD38-negative B cells (R2) were purified by sorting from high density tonsillar B cells (top). CD38-high (R3) and CD38-low (R4) B cells were purified by sorting from low density, CD39-negative tonsillar B cells (bottom). (B) The expression of SHP-1 and CD38 in the R2, R3, and R4 subpopulations of sorted tonsillar B cells was determined by ELISA and flow cytometry, respectively.
Mentions: We also quantitated SHP-1 expression by ELISA in purified GC B cells. Total CD38- and CD19-positive B cells that had been purified from five tonsils had SHP-1 concentration that ranged from 31 to 36% (mean 33%) of the concentration in CD38-negative, CD19-positive cells. GC B cells appeared to vary according to the intensity with which they stained for CD38 (Fig. 5). Therefore, we sorted GC B cells into CD38-high and -low populations, and compared their levels of SHP-1 to the levels in CD38-negative B cells. There was an inverse relationship between CD38 expression and SHP-1 content, with the highest CD38 expressing cells having a SHP-1 level that was only 20% that of CD38-negative cells (Fig. 6). CD38-positive B cells were also sorted on the basis of CD77 expression and assayed for SHP-1; CD77-positive and -negative GC B cells had identical and diminished levels of SHP-1, indicating that both centroblasts and centrocytes downregulate the PTPase (data not shown). In two of two experiments, CD38-negative, IgG-positive, CD19-positive B cells had the same concentration of SHP-1 as did resting, CD38-negative, CD19-positive B cells purified from the same donors (data not shown), suggesting that SHP-1 levels return to normal when GC cells differentiate into memory B cells.

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