Biomaterial Database

A theory of the ontogeny of the chicken humoral immune system: the consequences of diversification by gene hyperconversion and its extension to rabbit. 1993

R E Langman, and M Cohn

Developmental Biology Laboratory, Salk Institute, San Diego, CA 92138-9216.

The immune system's repertoire is generated in two stages: Stage I results in a small size high copy number repertoire that is diversified by "mutation" to result in a large size low copy number repertoire referred to as Stage II. The Stage I or high copy number repertoire is derived from information stored directly in the genome by two mechanisms. (a) The copy-cassette mechanism: the Ig-locus has one rearrangeable V gene segment which acts as recipient for controlled gene conversion in cis from a set of donor V gene segments that results in a family of subunits, L and H. This is illustrated by the avian systems. (b) The cassette-exchange mechanism: the Ig-locus has many rearrangeable V gene segments which are fused into transcription units, the products of which are a family of L and H subunits identical in function to those resulting from the copy-cassette mechanism. This is illustrated by the murine or human systems. It is possible for a species to use both mechanisms, copy-cassette at one Ig locus and cassette-exchange at the other Ig locus. This seems to obtain in the rabbit system. Further, it is possible to encode the high copy number repertoire directly in the genome as tandemly repeated rearranged transcription units as one sees in shark (a genomic analogue of the cassette-exchange mechanism). We have discussed here and elsewhere (Cohn and Langman, 1990) the consequences of these mechanisms for haplotype exclusion and functional responsiveness to antigen. The Stage I or high copy number repertoire generated by any of the above mechanisms is now a substrate for "mutation" which generates the low copy number or Stage II repertoire. These three species are compared in table V. The high copy number repertoire is small but the response to any antigen that it recognizes is rapid. The low copy number repertoire is large but responsiveness to any antigen it recognizes is slow. Cooperativity between the two repertoires optimizes the overall responsiveness with respect to rapidity of response and range of responsiveness. The use of a copy-cassette mechanism requires that the phi B cell undergoing gene conversion have a single rearranged L- and H-chain haplotype (L+/oH+/o). The reason is that conversion can correct an aberrantly rearranged transcription unit and generate an unacceptable level of doubles. In order to have one chromosome functionally rearranged and the homologue in the germline configuration, a selection mechanism is required.(ABSTRACT TRUNCATED AT 400 WORDS)

UI	MeSH Term	Description	Entries
D007107	Immune System	The body's defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components.	Immune Systems,System, Immune,Systems, Immune
D007136	Immunoglobulins	Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.	Globulins, Immune,Immune Globulin,Immune Globulins,Immunoglobulin,Globulin, Immune
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D011817	Rabbits	A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes.	Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D002060	Bursa of Fabricius	An epithelial outgrowth of the cloaca in birds similar to the thymus in mammals. It atrophies within 6 months after birth and remains as a fibrous remnant in adult birds. It is composed of lymphoid tissue and prior to involution, is the site of B-lymphocyte maturation.	Fabricius Bursa
D002642	Chick Embryo	The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching.	Embryo, Chick,Chick Embryos,Embryos, Chick
D002645	Chickens	Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA.	Gallus gallus,Gallus domesticus,Gallus gallus domesticus,Chicken
D005075	Biological Evolution	The process of cumulative change over successive generations through which organisms acquire their distinguishing morphological and physiological characteristics.	Evolution, Biological
D005785	Gene Conversion	The asymmetrical segregation of genes during replication which leads to the production of non-reciprocal recombinant strands and the apparent conversion of one allele into another. Thus, e.g., the meiotic products of an Aa individual may be AAAa or aaaA instead of AAaa, i.e., the A allele has been converted into the a allele or vice versa.	Polar Recombination,Polaron,Conversion, Gene,Conversions, Gene,Gene Conversions,Polar Recombinations,Polarons,Recombination, Polar,Recombinations, Polar