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Article

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.

C.C. Delibrias was a recipient of a postdoctoral fellowship from EEC, Human Capital and Mobility Programme, and of a grant from the Leukaemia Research Fund. J.E. Floettmann was supported by a grant from the Welsh Scheme for the Development of Health and Social Research. M. Rowe was supported by the Wellcome Trust. D.T. Fearon is a Principal Research Fellow of the Wellcome Trust.

¹ Abbreviations used in this paper: GC, germinal center; HEL, hen egg lysozyme; LCL, lymphoblastoid cell line; me^v/me^v, motheaten viable; mIg, membrane Ig; PTPase, phosphotyrosine phosphatase; RT, room temperature; tTA, tetracycline-controlled transactivator.

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