J. Exp. Med., Volume 186, Number 9, November 3, 1997 1575-1583

Downregulated Expression of SHP-1 in Burkitt Lymphomas and Germinal Center B Lymphocytes

By C. Charlotte Delibrias,^* J. Eike Floettmann, Martin Rowe, and Douglas T. Fearon^*

From the ^* Wellcome Trust Immunology Unit, Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge CB2 2SP, United Kingdom; and  Department of Medicine, University of Wales, College of Medicine, Heath Park, Cardiff CF4 4XX, United Kingdom

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 me^v/me^v 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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