Endogenous Ig production in mu transgenic mice. I. Allelic exclusion at the level of expression.
Our findings indicate that allelic exclusion is maintained in B cells that successfully rearrange and express and endogenous H chain gene, despite carrying a functionally rearranged H chain transgene (17.2.25 mu a). Cloned hybridomas having a functionally rearranged endogenous H chain gene as well as the transgene produce only endogenous gene products. Some of these hybridoma cultures, upon continuous growth, will secrete transgene as well as endogenous gene products. However, the two H chain polypeptides appear to be made by different cells. In each of three cases of such "double producer" lines examined, further subcloning at this time reveals two types of clones: those that secrete only transgene and those that secrete only endogenous H chains. The clones producing transgene product have lost the functionally rearranged endogenous H chain genes, whereas the clones producing endogenous gene products still contain both transgene and endogenous functionally rearranged H chain genes. These results indicate that hybridomas expressing endogenous Ig have transgene copies that are potentially functional but are reversibly silenced by an unknown mechanism and suggest that inhibition of transgene expression may be mediated by endogenous Ig gene expression.
Imanishi-Kari
T
T
Tufts University School of Medicine, Department of Pathology, Boston, MA 02111.
Bandyopadhay
S
S
Busto
P
P
Huang
C A
CA
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D015870:Gene Expression; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D006825:Hybridomas; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007075:Immunoglobulin M / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007136:Immunoglobulins / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data
D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D007136:Immunoglobulins