Synthesis and regulation of the two human complement C4 genes in stable transfected mouse fibroblasts

N. Miura, H. L. Prentice, P. M. Schneider, D. H. Perlmutter

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


The major histocompatibility complex-linked human complement C4 genes are highly homologous in primary structure but give rise to products which differ in complement-activating function. In order to examine the synthesis, function, and regulation of these two genes independently, cloned C4A and C4B genes were transfected into mouse fibroblast L-cells. In the stable transfected cell lines, C4A and C4B are synthesized, undergo a complex series of post-translational modifications, and each functions appropriately in activation of the classical complement pathway. A marked difference in the kinetics of complement component C1-mediated cleavage of the C4A- and C4B-α chains was demonstrated in the transfectants and may contribute to the differences in the intrinsic functional activity of the two C4 isotypes. In contrast to the expression of other complement genes which are affected during the hepatic 'acute phase response' (factor B, C3), the expression of C4 was not regulated by interleukin-1 or tumor necrosis factor. Interferon-γ, however, mediated a dose- and time-dependent increase in the expression of the C4 genes. Moreover, interferon had a significantly greater and longer-lasting effect on the synthesis of C4A than that of C4B. Differences in the expression and regulation of these two genes provide insight into the control of complement activation during inflammation.

Original languageEnglish
Pages (from-to)7298-7305
Number of pages8
JournalJournal of Biological Chemistry
Issue number15
StatePublished - 1987


Dive into the research topics of 'Synthesis and regulation of the two human complement C4 genes in stable transfected mouse fibroblasts'. Together they form a unique fingerprint.

Cite this