Expression of heavy chain-only antibodies can support B-cell development in light chain knockout chickens.
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.
['Schusser|Benjamin|B|', 'Collarini|Ellen J|EJ|', 'Pedersen|Darlene|D|', 'Yi|Henry|H|', 'Ching|Kathryn|K|', 'Izquierdo|Shelley|S|', 'Thoma|Theresa|T|', 'Lettmann|Sarah|S|', 'Kaspers|Bernd|B|', 'Etches|Robert J|RJ|', 'van de Lavoir|Marie-Cecile|MC|', 'Harriman|William|W|', 'Leighton|Philip A|PA|']
D000818:Animals D030801:Animals, Genetically Modified D000906:Antibodies D000917:Antibody Formation D001402:B-Lymphocytes D002454:Cell Differentiation D002645:Chickens D017353:Gene Deletion D015870:Gene Expression D055786:Gene Knockout Techniques D023061:Gene Order D018390:Gene Targeting D005822:Genetic Vectors D007143:Immunoglobulin Heavy Chains D007147:Immunoglobulin Light Chains D010950:Plasma Cells D000072417:Protein Domains
Antibodies B-cell development Knockout chickens Immunoglobulins