Downregulated expression of SHP-1 in Burkitt lymphomas and germinal center B lymphocytes.
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.
Delibrias
C C
CC
Wellcome Trust Immunology Unit, Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge CB2 2SP, United Kingdom.
Floettmann
J E
JE
Rowe
M
M
Fearon
D T
DT
D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology*; D002051:Burkitt Lymphoma / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects; D018858:Germinal Center / Q000166:cytology / Q000201:enzymology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D010957:Plasmids; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis* / Q000235:genetics; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D013752:Tetracycline / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
D047908:Intracellular Signaling Peptides and Proteins; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D013752:Tetracycline