Effects of immunoglobulin structure on Fc receptor binding: A mouse myeloma variant immunoglobulin with a γ2b-γ2a hybrid heavy chain having a complete γ2a Fc region fails to bind to γ2a Fc receptors on mouse macrophages

We report here the primary structure of an immunoglobulin heavy chain synthesized by ICR 16, a variant of the MPC mouse myeloma cell line. The ICR 16 heavy chain is a γ2b-γ2a hybrid, consisting of the C(H)1 domain of γ2b and the hinge, C(H)2, and C(H)3 domains of γ2a subclasses. The genetic mechanism by which ICR 16 occurred may be recombination, based on homologies in both coding and intervening sequences in γ2b and γ2a constant region genes. Although the Fc fragment of ICR 16 is completely γ2a-like and has been shown to bind to γ2a Fc receptors on mouse macrophages, the intact H₂L₂ molecule is unable to do so. Such an observation underscores the crucial role that conformation may play in the ability of immunoglobulins to carry out biologic functions.