Somatic diversification of the chicken immunoglobulin light-chain gene.
The bursa of Fabricius provides a unique organ for the study of lineage-specific development in a multicellular organism. Unlike mammalian B cells, B cells in the chicken develop in a single wave of differentiation, beginning with the commitment of progenitor cells to the B cell lineage between days 10 and 15 of embryogenesis. By day 18 of embryogenesis, all lymphoid progenitor cells capable of differentiation along the B cell lineage have migrated to the bursa of Fabricius. Following migration to the bursa, these lymphoid progenitors enter exponential growth and begin to populate each of the 10(4) bursal follicles. Between day 18 of embryogenesis and 2-4 weeks of age, B cells undergo a stage of bursal-dependent differentiation. By the end of this period, chickens are able to mount primary immune responses against virtually all antigens. In addition, by this time sufficient numbers of B cells have migrated from the bursa to peripheral lymphoid organs so that the B cell immune system can be maintained even if the bird is bursectomized. Bursectomy of chicks after 4 weeks of age has no long-term effects on the development and maintenance of the B cell immune system in adult birds. Because of the central nature of the surface Ig molecule to B cell development in mammals, the chicken IgL gene locus has been intensively studied during avian B cell development. The chicken IgL locus is a particular interest because it has only one V region capable of rearrangement. Rearrangement of the IgL gene is not dependent on the bursal environment. B cell progenitors rearrange their IgL gene between days 10-15 of embryogenesis, prior to migration to the bursa. IgL gene rearrangement occurs by a deletional mechanism in which a precise joining of the IgL recombination signal sequences leads to a circular episomal element. During this deletion it appears that single nonrandom bases are added to both the V and J coding segments. Subsequent V-J joining occurs at random. Most progenitor B cells appear to rearrange only a single IgL allele. The high frequency of in-frame alleles observed in avian B cell lines appears to result from the selective amplification of cells with productive IgL rearrangements during bursal development between days 12 and 18 of embryogenesis. To create an immunological repertoire, chickens must diversify the coding sequence of this single functional V gene segment during development.(ABSTRACT TRUNCATED AT 400 WORDS)
McCormack
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Department of Microbiology, Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor 48109.
Thompson
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CB
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D001483:Base Sequence; D002060:Bursa of Fabricius / Q000166:cytology / Q000276:immunology; D002645:Chickens / Q000235:genetics / Q000276:immunology*; D004247:DNA; D015322:Gene Rearrangement, B-Lymphocyte; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008969:Molecular Sequence Data
D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D004247:DNA