Schusser B1, Collarini EJ2, Pedersen D2, Yi H2, Ching K2, Izquierdo S2, Thoma T1, Lettmann S3, Kaspers B3, Etches RJ2, van de Lavoir MC2, Harriman W2, Leighton PA4. 2016. Eur J Immunol. 46(9):2137-48. doi: 10.1002/eji.201546171. Epub 2016 Aug 2.
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. firstname.lastname@example.org.
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.
© 2016 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Antibodies; B-cell development; Immunoglobulins; Knockout chickens