Expression of Lyn protein on human malignant lymphomas.

BACKGROUND

lyn is one of the src family genes encoding protein-tyrosine kinases, expressed preferentially in B lymphocytes and monocytes/macrophages. Its gene product, Lyn protein, is thought to participate in cell membrane-associated signal transduction on B lymphocytes by associating physically and functionally with membrane-bound IgM.

EXPERIMENTAL

DESIGN

To investigate the expression of Lyn on human malignant lymphomas (MLs), 50 ML biopsies, 12 ML samples maintained in mice with severe combined immunodeficiency, and 4 African Burkitt type cell lines were studied with the use of immunohistology, immunochemistry, and Southern blot analysis.

RESULTS

Among biopsy specimens, 27 of 27 B-MLs, 5 of 21 T-MLs, and 2 of 2 null-MLs were stained. In severe combined immunodeficiency mouse-maintained B-MLs, unlike biopsied B-MLs, 4 of 11 were found to be unstained. Further analysis disclosed that all 4 of these unstained B-MLs were the Epstein Barr virus transformed B cells proliferating in severe combined immunodeficiency mice and not the original ML cells, suggesting the presence of a specific mechanism down-regulating the Lyn protein in this group. One IgA+ IgM- B-ML and one IgG+ IgM- B-ML were stained by the antibody, indicating the possible existence of molecular mechanisms other than membrane-bound IgM that facilitate Lyn protein expression. Decrease of Lyn expression was also noted in 3 of 4 Epstein-Barr virus-positive African Burkitt's ML lines. Complementary Western blot analysis of 8 immunostained and 4 unstained MLs confirmed the immunohistologic findings. However Southern blot analysis showed that the lyn gene in Lyn-positive and -negative cases were apparently unchanged.

CONCLUSIONS

The level of Lyn expression in MLs reflects mainly their normal counterpart, whereas it can be expressed somewhat differently in some cases, especially in Epstein Barr virus-transformed MLs that occur in immunocompromised hosts, on which it is often down-regulated. This is the first report of Lyn expression on human MLs.