FUNCTIONAL-ACTIVITY OF CD44 ISOFORMS IN HEMATOPOIESIS OF THE RAT

Expression of CD44 is involved in the maturation as well as the homing of haemopoietic progenitor cells. Whether these processes are mediate d by CD44 standard (CD44s) or variant (CD44v) isoforms is unknown. To assign functional activities of CD44 in haemopoiesis of the rat to dis tinct isoforms, ligand binding of haemopoietic progenitor cells was in hibited by monoclonal antibodies recognizing an epitope on CD44s (0x50 ) or CD44 exon v6 (1.1ASML). The vast majority of rat bone marrow cell s (BMC) as well as stromal cells and non-adherent cells in long-term b one marrow culture (LTBMC) expressed CD44s. Bone marrow cells and non- adherent cells in LTBMC, but not the stromal cells, also contained a p opulation of large and granulated cells, which stained with anti-CD44v 6. In vivo and in vitro reconstitution experiments revealed that homin g of BMC as well as settlement on stromal elements was influenced excl usively by anti-CD44s, which also inhibited proliferation of progenito r cells. Anti-CD44v6 had no influence on homing and seeding, but inter fered with stroma formation and progenitor maturation. Finally, restor ation of functional activity of T-lineage cells was impaired in the pr esence of anti-CD44v6. The data indicate that CD44s and CD44v6 fulfill ed distinct functions in haemopoiesis of the rat. Although CD44s facil itated homing and expansion of stern cells/progenitor cells, CD44v6 wa s involved in differentiation processes, particularly of lymphoid prog enitor cells.