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J. Exp. Med.,
Volume 189, Number 10, May 17, 1999 1611-1620
Locus Is Similarly Well
Expressed in Mice and Humans
By
From the Laboratory of Developmental Immunology, The Babraham Institute, Babraham, Cambridge
CB2 4AT, United Kingdom
Transgenic mice carrying a 380-kb region of the human immunoglobulin (Ig) 
light (L) chain
locus in germline configuration were created. The introduced translocus on a yeast artificial chromosome (YAC) accommodates the most proximal Ig variable region (V) gene cluster, including 15 V genes that contribute to >60% of L chains in humans, all J-C segments,
and the 3' enhancer. HuIgYAC mice were bred with animals in which mouse Ig
production was silenced by gene targeting. In the 
/ background, human Ig was expressed by
~84% of splenic B cells. A striking result was that human Ig was also produced at high levels
in mice with normal locus. Analysis of bone marrow cells showed that human Ig and mouse
Ig were expressed at similar levels throughout B cell development, suggesting that the Ig translocus and the endogenous locus rearrange independently and with equal efficiency at the
same developmental stage. This is further supported by the finding that in hybridomas expressing human Ig the endogenous L chain loci were in germline configuration. The presence of
somatic hypermutation in the human V genes indicated that the Ig-expressing cells function
normally. The finding that human genes can be utilized with similar efficiency in mice and
humans implies that L chain expression is critically dependent on the configuration of the locus.
translocus;
light chain expression levels;
pre-B cell activation;
V gene usage;
hypermutation
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