Immunoglobulin biosynthesis by the MOPC 173 mouse myeloma tumor and a variant spleen clone.

The IgG2a producing MOPC 173 tumor synthesizes heavy (H) and light (L) chains and assembles them into H2L2 utilizing heavy chain dimers (H2) and H2L as the major precursors. Although the tumor cells secrete only H2L2, they synthesize excess L chains which appear to be degraded and are not secreted. A L chain-producing variant arising spontaneously from the MOPC 173 tumor also failed to secrete any L chains. MOPC 173 tumor cells were cloned in the spleens of normal BALB/c mice and 1 of 23 spleen clones appeared to differ from the parent tumor in demonstrating a) a transient block in the assembly of H2L2 at the H2 level, leading to delayed formation and secretion of H2L2, b) appreciable amounts of non-covalently bonded H2L, c) an abnormal intracellular immunoglobulin species, H4, d) production of equimolar amounts of H and L chains. The patterns of immunoglobulin synthesis and assembly demonstrable in the above studies were also observed when tumor cells were studied in situ. Tryptic peptide mapping of the H and L chains produced by the MOPC 173 tumor and the variant spleen clone failed to demonstrate any differences in the H chains, but there were definite chemical differences in the L chains. These studies indicate that variant myeloma cells producing structurally altered immunoglobulins may continually be arising in myeloma tumors.