Mouse myeloma cells that make short immunoglobulin heavy chains: Pleiotropic effects on glycosylation and chain assembly

Two variants in immunoglobulin heavy chain production, derived from the MPC 11 mouse myeloma cell line, make short heavy (H) chains with identical precise deletions of the C(H)3 domain. The C(H)3 domain is expressed in the H chain mRNA from both variants. Although in vitro translation of this mRNA produces one H chain species, deleted heavy chains are secreted as heavy-light (HL) and H₂L₂ moieties in contrast to MPC 11, which secretes only H₂L₂. The heavy chains of HL apparently contain more carbohydrate (CHO⁺) than do the H chains of H₂L₂, and inhibition of N-linked glycosylation results in the secretion of relatively more H₂L₂. Here we present evidence suggesting that (a) the absence of the C(H)3 domain has led to conformational changes in these molecules, (b) these changes permit posttranslational glycosylation, and (c) unrestrained glycosylation can frequently yield unusual CHO⁺ structures that make complete assembly unlikely.