Complement activation by IgM: evidence for the importance of the third constant domain of the μ heavy chain

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Abstract
We have isolated and analyzed the DNA encoding the μ heavy chain constant region of a mutant IgM which is defective in initiating complement-dependent cytolysis. By assaying the expression of μ genes which were constructed in vivo from mutant and normal gene segments, we have mapped the mutation into a 555-base pair segment. In this segment there is one nucleotide change, such that the mutant μ gene encodes serine rather than the normal proline at amino acid position 436 in the third constant domain. We have used site-directed mutagenesis to revert this mutation to the normal sequence and shown that this substitution results in the production of IgM with the normal phenotype.