Influence of the Isotype of the Light Chain on the Properties of IgG

Abstract

It is widely appreciated that the isotype of the H chain of the Ab molecule influences its functional properties. We have now investigated the contribution of the isotype of the L chain to the structural and functional properties of the Ab molecule. In these studies, the L chain variable region of a murine anti-dansyl Ab was joined to either human κ or λ constant region domains and expressed with mouse-human chimeric H chains of the four human IgG isotypes. The resulting Abs were secreted as fully assembled molecules although, as has been previously observed, IgG4 with either κ or λ L chains was also secreted as HL half-molecules. However, the isotype of the L chain can influence the kinetics of intracellular assembly with IgG1λ, IgG2λ, and IgG4λ assembling more slowly than their κ counterparts. The isotype of the L chain also influenced the susceptibility of the interchain disulfide bonds to attack by reducing agents with variable effects, depending on the isotype of the H chains. For IgG2, but not for IgG1, -3, and -4, the isotype of the L chain influenced the rate of clearance in mice, with IgG2λ having a shorter in vivo half-life than IgG2κ. Only slight differences were also observed between λ and κ molecules in their kinetics of binding to and dissociation from the hapten dansyl. These studies demonstrate that the isotype of the L chain has only a slight impact on the structural and functional properties of variable region identical Abs.

Structural and Functional Characterization of Disulfide Isoforms of the Human IgG2 Subclass

“…Although deposited 1HZH coordinates were numbered in Kabat and Wu format, the residue numbering in this figure is in Eu format, the same as in Table 1 equal amounts for IgG2 and IgG2. Previous reports (4,32,33) have shown that the LC type can impact antigen/receptor binding and in vivo clearance. Some of these results were linked to specific differences in flexibility between the -and -LC, and, as we have shown in this report, may also be attributed to different distribution of IgG2 isoforms.…”

Evolutionary redefinition of immunoglobulin light chain isotypes in tetrapods using molecular markers

“…Yet another well-established functional difference between and antibodies is the interaction of chains with the bacterial surface protein L (20,24). It has also been demonstrated that the isotype of the IGL chain can influence the kinetics of the intracellular assembly of antibodies and the susceptibility of the interchain disulfide bonds to reducing agents (25). A different kind of functional differentiation between and antibodies was indicated by Wardemann et al (2004) (26).…”

Considerations in producing preferentially reduced half-antibody fragments

“…However, although class IgG antibodies are quite a homogeneous population, there are structural differences among the subclasses in one species (Montano and Morrison 2002) and among antibodies derived from different hosts. Interestingly, the biggest structural variations have been observed in the hinge region and the Fc fragment (Kabat 1967).…”