DOWN-REGULATED EXPRESSION OF SHP-1 IN BURKITT-LYMPHOMAS AND GERMINAL CENTER B-LYMPHOCYTES

We wish to identify developmental changes in germinal center B cells t hat may contribute to their rapid growth. SHP-1 is an SH2 domain-conta ining phosphotyrosine phosphatase that negatively regulates activation of B cells and other cells of hematopoietic lineages. We have found t hat in all 13 EBV-negative and 11 EBV-positive Burkitt lymphomas with a nonlymphoblastoid phenotype, the mean concentration of SHP-1 was red uced 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 phen otype of Burkitt lymphomas was supported by the low to absent immunofl uorescent staining for SHP-1 in germinal centers, and by the inverse r elationship between the concentration of SHP-1 and the expression of t he 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 cel ls 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 dysr egulated, spontaneous signaling by cytokine and antigen receptors. The refore, germinal center B cells may have a developmentally regulated, low threshold for cellular activation.