Assembled IgG molecules are exported from the endoplasmic reticulum in myeloma cells despite the retention signal SEKDEL.

The KDEL retention signal, when added at the C-terminal of the constant region of light and heavy chains of immunoglobulins is able to efficiently retain assembled immunoglobulins only in cells of nonlymphoid origin. In transfected myeloma cells the wild type and the KDEL-Ig mutants are secreted with the same efficiency. This phenomenon is not due to a proteolytic cleavage of the KDEL signal nor to a lack of intermolecular disulfide bond formation and is not due to an impaired recognition of the KDEL signal in myeloma cells. Thus, the constitutive secretion of assembled immunoglobulins, currently considered to follow a default process, appears to be regulated by a mechanism that is able to overcome an efficient ER retention system.