Immunoglobulin Heavy Chain Switching in Cultured I.29 Murine B Lymphoma Cells: Commitment to an IgA or IgE Switch

Abstract

A clone of B cells bearing IgM can be induced to switch to the expression of other isotypes, i.e. to other C_H genes, while maintaining expression of the identical heavy chain variable region (V_H) gene. Studies of the structure of Ig genes in myelomas (Davis et al., 1980), in hybridomas (Hurwitz et al., 1980), and in a B cell lymphoma (Stavnezer et al., 1982) which have undergone isotype switching, and also in normal splenic B cells treated with 1ipopolysaccharide (LPS) (Hurwitz and Cebra, 1982) indicate that DNA recombinations between tandemly repeated switch (S) sequences located 5’ to each C_H gene except δ result in the deletion of the µ gene and the other C_H genes located 5′ to the C_H gene to be expressed, and effect the isotype switch. The production of δ is an exception, as cloned cell lines which produce µ and δ simultaneously contain δ genes in the same context as in µ — producing cells and must produce µ and δ by alternative RNA processing. Other investigators have questioned whether alternative RNA processing may be used to express other H chains simultaneously with µ (Yaoita et al., 1982) in order to explain the surprisingly large number of cells in the spleen which express two isotypes simultaneously (~5% of spleen cells). But because H chain switching can occur rapidly and frequently, partly because the target for switch recombination is large, it is entirely possible that the double-producing cells are cells which have recently deleted their µ genes but still have y mRNA and protein.