The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/5/1611/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 10, May 17, 1999 1611-1620

Articles

A Human Immunoglobulin {lambda} Locus Is Similarly Well Expressed in Mice and Humans

Andrei V. Popov, Xiangang Zou, Jian Xian, Ian C. Nicholson, and Marianne Brüggemann

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) {lambda} light (L) chain locus in germline configuration were created. The introduced translocus on a yeast artificial chromosome (YAC) accommodates the most proximal Ig{lambda} variable region (V) gene cluster, including 15 V{lambda} genes that contribute to >60% of {lambda} L chains in humans, all J{lambda}-C{lambda} segments, and the 3' enhancer. HuIg{lambda}YAC mice were bred with animals in which mouse Ig{kappa} production was silenced by gene targeting. In the {kappa}–/– background, human Ig{lambda} was expressed by ~84% of splenic B cells. A striking result was that human Ig{lambda} was also produced at high levels in mice with normal {kappa} locus. Analysis of bone marrow cells showed that human Ig{lambda} and mouse Ig{kappa} were expressed at similar levels throughout B cell development, suggesting that the Ig{lambda} translocus and the endogenous {kappa} 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{lambda} the endogenous L chain loci were in germline configuration. The presence of somatic hypermutation in the human V{lambda} genes indicated that the Ig{lambda}-expressing cells function normally. The finding that human {lambda} 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.

Key Words: human Ig{lambda} translocus • light chain expression levels • pre-B cell activation • V gene usage • hypermutation

Address correspondence to Marianne Brüggemann, Laboratory of Developmental Immunology, Department of Development and Genetics, The Babraham Institute, Babraham, Cambridge CB2 4AT, UK. Phone: 44-1223-496-304; Fax: 44-1223-496-030; E-mail: marianne.bruggemann{at}bbsrc.ac.uk

A.V. Popov and X. Zou contributed equally to this work.

Abbreviations used: ES, embryonic stem; Hu, human; N, nonencoded; P, palindromic; PFGE, pulsed-field gel electrophoresis; PNA, peanut agglutinin; PP, Peyer's patch; RACE, rapid amplification of cDNA ends; RSS, recombination signal sequence(s); RT, reverse transcriptase; TdT, terminal deoxyribonucleotide transferase; YAC, yeast artificial chromosome.


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