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Expression of heavy chain-only antibodies can support B-cell development in light chain knockout chickens.

Posted by on in 2016
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Schusser B1Collarini EJ2Pedersen D2Yi H2Ching K2Izquierdo S2Thoma T1Lettmann S3Kaspers B3Etches RJ2van de Lavoir MC2Harriman W2Leighton PA42016. Eur J Immunol. 46(9):2137-48. doi: 10.1002/eji.201546171. Epub 2016 Aug 2.

1Reproductive Biotechnology, Technische Universität München, WZW Center of Life Science, Freising-Weihenstephan, Germany.
2Crystal Bioscience Inc, Emeryville, CA, USA.
3Department of Veterinary Science, Institute for Animal Physiology, Ludwig-Maximilians-Universitaet Muenchen, Munich, Germany.
4Crystal Bioscience Inc, Emeryville, CA, USA.



Since the discovery of antibody-producing B cells in chickens six decades ago, chickens have been a model for B-cell development in gut-associated lymphoid tissue species. Here we describe targeting of the immunoglobulin light chain locus by homologous recombination in chicken primordial germ cells (PGCs) and generation of VJCL knockout chickens. In contrast to immunoglobulin heavy chain knockout chickens, which completely lack mature B cells, homozygous light chain knockout (IgL(-/-) ) chickens have a small population of B lineage cells that develop in the bursa and migrate to the periphery. This population of B cells expresses the immunoglobulin heavy chain molecule on the cell surface. Soluble heavy-chain-only IgM and IgY proteins of reduced molecular weight were detectable in plasma in 4-week-old IgL(-/-) chickens, and antigen-specific IgM and IgY heavy chain proteins were produced in response to immunization. Circulating heavy-chain-only IgM showed a deletion of the CH1 domain of the constant region enabling the immunoglobulin heavy chain to be secreted in the absence of the light chain. Our data suggest that the heavy chain by itself is enough to support all the important steps in B-cell development in a gut-associated lymphoid tissue species.


Antibodies; B-cell development; Immunoglobulins; Knockout chickens

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