Vitamin B₁₂-binding Protein of Leukocytes as a Possible Major Source of the Third Vitamin B₁₂-binding Protein of Serum

Much evidence suggests that granulocytes are a major source of serum vitamin B₁₂-binding protein (BBP). The latter has three components: α-1-globulin BBP (Transcobalamin I, TC I), β-globulin BBP (TC II), and a recently described third BBP. Granulocytic BBP has appeared to be identical to TC I except in electrophoretic mobility. In the present study, the dominant BBP of leukocyte extracts from subjects with and without myeloproliferative disease behaved like the third serum BBP. With a few exceptions, more than half the leukocytic binder eluted with the "β globulins" on rapid DEAE-cellulose chromatography. At pH 8.6, electrophoretic mobility of the leukocytic BBP was always α₂ or β. At ph 4.5, normal and chronic myelogenous leukemia leukocytic BBP, unlike TC I and TC II, showed little electrophoretic migration. These findings suggest that leukocytic BBP is probably heterogenous and that its major component resembles the third serum BBP more than it does TC I. The third serum BBP, levels of which are elevated in some states of leukocytic proliferation, may derive directly from mature granulocytes. TC I may arise by addition of sialic acid to the third (granulocytic) BBP under certain circumstances or be released from other cells, such as less mature granulocytes. Much of the confusion in the literature regarding source and significance of serum BBP may relate to separating it into only two fractions (α globulin and "β globulin," or "TC I" and TC II) instead of into three fractions.