Allelic exclusion in transgenic mice expressing a heavy chain disease‐like human μ protein

Abstract

Heavy chain diseases (HCD) are neoplastic proliferations of B cells which secrete truncated immunoglobulin heavy chains without associated light chains. These proteins are encoded by mutated genes which may also give rise to truncated membrane immunoglobulins. The neoplastic cells proliferate in vivo although they cannot bind any antigen, due to deletions in the variable domain of their antigen receptors. The reason for the clonal proliferation of HCD cells and the biological effects of the truncated membrane-bound chains are presently unknown. We wanted to determine whether the expression of HCD proteins would interfere with B cell development. To this end we made transgenic mice with a human mu gene, lacking the VDJ exon, that encodes a protein similar to that produced in two cases of HCD. Transgenic mice were also produced with a similar construct but encoding only the membrane-bound form of the truncated mu chain. Transgene encoded C mu proteins are expressed on the cell surface without associated light chains and are responsible for allelic exclusion of murine heavy chains.