Activity of multiple light chain genes in murine myeloma cells producing a single, functional light chain

Abstract

Two cloned lambda 1-producing myelomas (HOPC-1, MOPC-104E) contain rearranged kappa genes and levels of mature-sized kappa RNA comparable to those found in kappa-producing myeloma cells. Another lambda 1-producing myeloma tumor line (HOPC-2020) and a lambda 1-containing B cell leukemia line (BCL1) also contain significant levels of kappa RNA. One lambda 11-producing line (MOPC-315) contains no detectable kappa RNA, but it also has no kappa genes in the embryonic configuration. kappa-related proteins are not detectable in the lambda 1-producing lines by standard procedures, but by sensitive methods at least two lines contain kappa protein fragments. The MOPC-104E line produces both a 14.5K kappa fragment that is not readily detectable because of its low rate of synthesis and short half-life (T 1/2 less than 5 min), and a major 16.5K protein that lacks kappa cross reactivity but is demonstrable by translation of purified MOPC-104E kappa RNA. The HOPC-1 kappa RNA also encodes a short-lived 14K kappa fragment. The MPC-11 line, which produces a mature kappa RNA and protein as well as an 800 base kappa fragment RNA and kappa protein fragment, has both kappa alleles rearranged, one apparently aberrantly between J and C kappa. Two different kappa RNA species, one the same size as the MPC-11 kappa fragment RNA, frequently are present in kappa RNA-containing Abelson murine leukemia virus-transformed lymphoid cells as well as in 18 and 19 day murine fetal liver. For light chains, neither allelic nor isotype exclusion is generally evident in myeloma and lymphoma cells; rather both produce only a single functional light chain. Models of light chain activation must explain restriction by considering the functional properties of the light chain rather than light chain gene expression.