In vivo trafficking and catabolism of IgG1 antibodies with Fc associated carbohydrates of differing structure

We have now produced mouse-human chimeric IgG1 in wild-type Chinese hamster ovary (CHO) cell lines Pro-5 as well as in the glycosylation mutants Lec 2 , Lec 8, and Lec 1. Analysis of the attached carbohydrates shows those pres ent on IgG1-Lec1 were mannose terminated, Carbohydrate present on IgG1-Lec8 was uniformly biantennary terminating in N-acetylglucosamine. The glycosgl ation profiles of IgG1-Lec 2 and IgG1-Pro-5 were heterogeneous. Only IgG1-P ro-5 was sialylated with sialic acid present on only a small percentage of the carbohydrate structures. When the in vivo fate of antibodies labeled wi th I-125-lactotyramine was determined, it was found that the majority of al l of the antibodies, irrespective of the structure of their attached carboh ydrate, is catabolized in the skin and muscle. However, the attached carboh ydrate structure does influence the amount that is catabolized in the liver and the liver serves as a major site for the catabolism of proteins bearin g carbohydrate with the Lec2 (with terminal galactose) or Lec1 (with termin al mannose) structure.