CD40 is a surface molecule expressed on B lymphocyte lineage cells, and plays an important role in B-cell differentiation and activation. We have previously demonstrated that antibodies to CD40 could inhibit aggressive histology human B lymphoma cell lines by inducing activation induced cell death. A soluble recombinant murine CD40 ligand (rmCD40L) was then tested on the A.20 murine B-cell lymphoma line. Incubation with rmCD40L resulted in significant growth inhibition of A.20 cells by [3H]-thymidine incorporation assay (80.0% inhibition at 1/ig/ml of rmCD40L). Crosslinking of the rmCD40L using anti-leucine zipper resulted in even greater inhibition of proliferation significantly (90.6% inhibition at 1/ig/ml ofrmCD40L). Incubation with crosslinked rmCD40L significantly increased apoptotic cell population in the A.20 cell line with the cell population in the <2N DNA peak increasing (20.2% vs 61.3%). We then determined the antitumor effects of rmCD40L in vivo using a bone marrow transplantation model. BALB/c mice were injected 2×105 of A.20 cells i.v. on day -2. The mice then received lethal irradiation and syngeneic bone marrow cells on day 0 and were injected with 50/ig of rmCD40L i.p. on day 1, 2. Treatment with rmCEMOL significantly (p < 0.05) prolonged the survival of the recipients. Thus, stimulation of CD40 by its ligand after BMT may offer a biologic approach to the treatment of B-cell lymphomas.
|Original language||English (US)|
|State||Published - 1996|
ASJC Scopus subject areas
- Agricultural and Biological Sciences (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)
- Cell Biology