Ectodomain shedding of CD200 from the B-CLL cell surface is regulated by ADAM28 expression

CD200, a membrane glycoprotein of the immunoglobulin superfamily, is overexpressed in CLL. Soluble in serum CD200 (sCD200) is correlated with poor prognosis in CLL.ADAM (a disintegrin and metalloproteinase) enzymes are implicated in membrane protein shedding. ADAM28 mRNA expression in CLL was correlated with plasma sCD200 levels, and release into culture from CLL cells. siRNA for ADAM28 decreased release of sCD200 from cultures and transfection of a cloned ADAM28 gene into CD200+ cells enhanced release of sCD200.Our data support the hypothesis that ADAM28 plays a role in the shedding of CD200 from B-cell CLL cells.