Somatically generated mouse myeloma variants synthesizing IgA half-molecules.

Abstract

Whereas mouse myelomas that secrete IgA half-molecules have been shown to arise in vivo, their origin has not been deinitely established. Somatic variants secreting phenotypicaly similar molecules are shown to arise directly from the normal IgA-secreting myelomas S107 and W3082. In addition to being improperly assembled, the variant proteins have distinct carboxy-terminal deletions and an abberrant HL chain disulfide bond. For at least one of the variants, variable region serology and affinity for hapten are both unaffected by these changes. Southern and Northern blot analyses indicate normal size DNA restriction fragments and mRNA, suggesting premature termination as the mechanism of deletion. These results are discussed in relation to possible mutational hot spots and long-range interdomain interactions.