Generation of heavy-chain-only antibodies in mice

被引:59
作者
Janssens, Rick
Dekker, Sylvia
Hendriks, Rudi W.
Panayotou, George
van Remoortere, Alexandra
San, John Kong-a
Grosveld, Frank
Drabek, Dubravka
机构
[1] ErasmusMC, Dept Cell Biol, NL-3000 CA Rotterdam, Netherlands
[2] ErasmusMC, Dept Immunol, NL-3000 CA Rotterdam, Netherlands
[3] Biomed Sci Res Ctr, Varkiza 16602, Greece
[4] Leiden Univ, Med Ctr, Dept Parasitol, NL-2333 ZA Leiden, Netherlands
关键词
immunoglobulin rearrangement; transgenic;
D O I
10.1073/pnas.0601108103
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We have generated transgenic mice containing hybrid llama/human antibody loci that contain two llama variable regions and the human D, J, and C mu and/or C gamma constant regions. Such loci rearrange productively and rescue B cell development efficiently without LC rearrangement. Heavy-chain-only antibodies (HCAb) are expressed at high levels, provided that the CH1 domain is deleted from the constant regions. HCAb production does not require an IgM stage for effective pre-B cell signaling. Antigen-specific heavy-chain-only IgM or IgGs are produced upon immunization. The IgG is dimeric, whereas IgM is multimeric. The chimeric HCAb loci are subject to allelic exclusion, but several copies of the transgenic locus can be rearranged and expressed successfully on the same allele in the same cell, Such cells are not subject to negative selection. The mice produce a full antibody repertoire and provide a previously undescribed avenue to produce specific human HCAb in the future.
引用
收藏
页码:15130 / 15135
页数:6
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