Immunoglobulin genes

30 Mar

Immunoglobulin genes


Diagram of a typical IgG molecule. Within each immunoglobulin molecule, the two L chains are identical and the two H chains are identical. Numbers represent approximate amino acid residues from the N terminus of the respective chain.

tain identical L and H chains. See Appendix C, 1939, Tiselius and Kabat; 1959, Edelman; 1962, Porter; 1965, Hilschmann and Craig; 1969, Edelman et al.; 1976, Hozumi and Tonegawa; 1977, Silverton, Navia, and Davies; 1987, Tonegawa; abzymes, B lymphocyte, glycosylation, hybridoma, IgA, IgM, im- mune response, monoclonal antibodies, oligosaccha- ride, V(D)J recombination. immunoglobulin chains the components of the heteropolymeric immunoglobulin molecules.

There are five groups of heavy chains, each characteristic of a specific class of immunoglobulin: gamma (IgG), mu (IgM), epsilon (IgE), alpha (IgA), and delta (IgD). The genes encoding all the heavy immuno- globulin chains are located on human chromosome 14. The constant region of each heavy chain makes up about three-fourths of the molecule, and the gene segments encoding the constant regions are ar- ranged in the sequence mu, delta, gamma, epsilon, and alpha in both humans and mice. There are two groups of light chains: kappa chains, encoded by gene segments on human chromosome 2, and lambda chains, encoded by gene segments on chro- mosome 22.

See immunoglobulin genes. immunoglobulin domain superfamily a group of glycoproteins that are embedded in the surface of the membranes of certain cells and which have one or more immunoglobulin domains. Each domain is a chain of about 100 amino acids that folds back and forth upon itself to form a sandwich of two pleated sheets linked by a disulfide bond. Included in the su- perfamily are the immunoglobulins (q.v.) with up to 12 domains per molecule, the T cell receptors (q.v.), and the MHC receptors (q.v.), each with two do- mains per molecule, and the CD4 and CD8 recep- tors (q.v.) with four domains and a single domain, respectively.

The genes that encode these proteins are assumed to have evolved from a common ances- tral gene over a period of hundreds of millions of years. immunoglobulin genes genes encoding the light and heavy chains of the immunoglobulins. These genes are remarkable in that they are made up of segments that are shuffled as the B lymphocytes ma- ture. The light chains contain segments that can be symbolized L-V, J, and C. The V, or variable, seg- ment codes for the first 95 amino acids of the chain, whereas the C, or constant, segment codes for amino

Immunological memory

acids 108 to 214. The joining segment, J, codes for amino acids 96 to 107. L codes for a leader sequence 17-20 amino acids long; it functions in the transport of the molecule through the plasmalemma and is cleaved off the molecule in the process. There are about 300 L-V segments per light chain gene, and each of the V segments has a different base se- quence. In the kappa gene, there are six J segments, each with a different base sequence, and one C seg- ment.

During differentiation of a given B lympho- cyte stem cell, an immunoglobulin gene is assembled containing one L-V, one J, and one C segment, and this gene is transcribed by the lymphocyte and all of its progeny. The lambda gene also contains about 300 L-V segments, but each of the six J segments has its own adjacent C segment. The heavy chain gene is over 100,000 nucleotides long and contains a series of segments that can be symbolized L-V, D, J, Cµ, Cδ, Cγ3,Cγ1,Cγ2b, Cγ2a, Cε, and Cα. There are about 300 L-V segments, 10-50 D segments, 4 J segments, and one each of the C segments. Each D segment codes for about 10 amino acids. During dif- ferentiation the segments are shuffled so that the variable region of a heavy chain is encoded by a seg- ment that contains one L-V, one D, and one J seg- ment.

The gene also contains mu, delta, gamma, ep- silon, and alpha subsegments, and which one of these is transcribed determines the class to which the antibody will belong. See Appendix C, 1965, Dreyer and Bennett; 1976, Hozumi and Tonegawa; 1981, Sakano et al..; 1987, Tonegawa; allelic exclu- sion, genomic equivalence, heavy chain class switch- ing, immunoglobulin chains, transfectoma, V(D)J re- combination. immunological memory the capacity of the im- mune system to respond more rapidly and more vig- orously to the second contact with a specific antigen than observed in the primary response to the first contact; the booster or anamnestic response. immunological suppression a genetic or induced condition in which the ability of an individual’s im- mune system to respond to most or all antigens is impaired.

See specific immune suppression. immunological surveillance theory the theory that the cell-mediated immune system evolved pri- marily to continuously monitor the body for sponta- neously arising cancerous cells or those containing foreign pathogens and to destroy them. immunological tolerance a state of nonreactivity toward a substance that would normally be expected to elicit an immune response. Tolerance to specific foreign antigens can be induced by the exposure of a bird or mammal to the foreign antigens during em- bryonic or neonatal (depending upon species) life. In adults, tolerance (usually of shorter duration) can be induced by using particular routes of administration for the antigens or administration of agents that are particularly effective against cells proliferating in re- sponse to antigen.

Mechanisms may include actual deletion of potentially reactive lymphocytes or their “inactivation” by immunological suppression. See Appendix C, 1945, Owen; 1953, Billingham et al. immunology the science dealing with immunity, serology, immunochemistry, immunogenetics, hy- persensitivity, and immunopathology. See Appendix C, 1778, Jenner; 1900, Ehrlich; 1930, Landsteiner; cellular immunity. immunoselection a method for isolating cell-line variants lacking certain antigens, such as those of the major immunogene complex. By treating cells with a specific antiserum and complement, all cells die, except a few spontaneously arising variants. These do not express the corresponding antigen, and there- fore they live and can be isolated.

Many of these variants appear to be due to deletion mutations rather than to epigenetic changes or mitotic cross- ing-over. Compare with antigenic conversion. impact theory a proposal, published in 1984 by Walter Alvarez and five colleagues, that the mass ex- tinction of various groups of organisms that occured at the end of the Cretaceous (q.v.) resulted from the collision of the earth with an asteroid or comet. Rocks at the Cretaceous-Tertiary boundary have high iridium concentrations, and this iridium is pos- tulated to have arisen from the pulverized asteroid. impaternate offspring an offspring from parthe- nogenetic reproduction in which no male parent took part. See parthenogenesis. imperfect excision the release of a genetic ele- ment (e.g., an insertion sequence or prophage) from a DNA molecule in a way that either includes more than or less than the element itself. imperfect flower See flower. implant material artificially placed in an organism, such as a tissue graft, an electronic sensor, etc. implantation 1. attachment of a mammalian em- bryo to the uterine wall. 2. the addition of tissue grafts to an organism without the removal of any- thing from it. imprinting 1. the imposition of a stable behavior pattern in a young animal by exposure, during a par- ticular period in its development, to one of a re- stricted set of stimuli. 2. See parental imprinting.


inactivation center a region of the mouse X chro- mosome that governs the degree to which translo- cated autosomal genes are inactivated when the as- sociated X-linked genes are inactivated as the result of random X-inactivation. See Cattanach’s transloca- tion, Lyon hypothesis. inactive X hypothesis Lyon hypothesis (q.v.).

Inarticulata a division of invertebrates containing the unsegmented, coelomate protostomes, such as sipunculids and molluscs. See Appendix A. inborn error a genetically determined biochemical disorder resulting in a metabolic defect that pro- duces a metabolic block having pathological conse- quences. See Appendix C, 1909, Garrod. inbred strain a group of organisms so highly in- bred as to be genetically identical, except for sexual differences. See isogenic, mouse inbred lines.

inbreeding the crossing of closely related plants or animals. inbreeding coefficient See Wright’s inbreeding co- efficient. inbreeding depression decreased vigor in terms of growth, survival, or fertility following one or more generations of inbreeding. incapsidation the construction of a capsid around the genetic material of a virus. inclusive fitness See Hamilton’s genetical theory of social behavior. incompatibility in immunology, genetic or anti- genic differences between donor and recipient tis- sues that evoke an immunological rejection response.

incomplete dominance failure of a dominant phe- notype to be fully expressed in an organism carrying a dominant and a recessive allele. The result is usu- ally a phenotype that is intermediate between the homozygous dominant and the recessive forms. the term is synonymous with partial dominance and semidominance. See dominance. incompletely linked genes genes on the same chromosome that can be recombined by crossing over. incomplete metamorphosis See Hemimetabola. incomplete sex linkage the rare phenomenon of a gene having loci on the homologous segments of both X and Y chromosomes. See XY homology. 

incross mating hetween individuals from the same inbred line or variety, often of the same genotype. incubation period the period over which eggs, cells, and so forth are incubated; the period between exposure to an infection and the appearance of the first symptoms. indels an acronym for insertions and deletions. The term often appears in studies of the mechanisms that cause genomic divergence between related spe- cies. See sequence similarity estimates. independent assortment the random distribution to the gametes of genes located on different chromo- somes.

Thus, an individual of genotype Aa Bb will produce equal numbers of four types of gametes: AB, Ab, aB, and ab. See Mendel’s laws. independent probabilities in a group of events, the occurrence of any one event having no influence on the probability of any other event. For example, the orientation of one pair of homologous chromo- somes on the first meiotic metaphase plate does not influence the orientation of any other pair of homo- logs.

See independent assortment. indeterminant inflorescence an inflorescence, such as a raceme (q.v.), in which the first flowers to open are at the base and are followed upward by progres- sively younger ones. index case a synonym for propositus (q.v.). index fossil a fossil that appears only in rocks of a relatively limited geological age span. indigenous referring to a species that colonized a specific area, such as an island, without human inter- vention. However, the species lives naturally in other places as well. Contrast with endemic. indirect immunofluorescence microscopy See immunofluorescence. indoleacetic acid auxin, a phytohormone. See auxins.

indolephenoloxidase an earlier name for the en- zyme now called superoxide dismutase (q.v.). Indrichotherium the largest mammal ever to walk the earth. It belonged to the rhinoceros family and lived in Asia during the Oligocene (q.v.).

Induced mutation

induced mutation a genetic alteration produced by exposure to a mutagen. Compare with spontane- ous mutation. inducer any of the small organic molecules that cause the cell to produce larger amounts of the en- zymes involved in their metabolism. Inducers are a class of effector molecules (q.v.). See gratuitous in- ducer, regulator genes. inducible enzyme an enzyme synthesized only in response to an inducer. See adaptive enzyme, regula- tor gene.

inducible system a regulatory system in which the product of a regulator gene (the repressor) is active and blocks transcription of the operon. The effector (called an inducer) inactivates the repressor and therefore allows mRNA synthesis to occur. Thus, transcription occurs only in the presence of effector molecules. See regulator gene. Compare with repress- ible system. induction 1. the determination of the develop- mental fate of one cell mass by another.

The mor- phogenic effect is brought about by an evocator act- ing upon competent tissue. 2. the stimulation of a lysogenized bacterium to produce infective phage. 3. the stimulation of synthesis of a given enzyme in re- sponse to a specific inducer. See Appendix C, 1924, Spemann and Mangold. inductor any substance that carries out an induc- tion similar to that performed by an organizer (q.v.). industrial melanism the phenomenon where me- lanic morphs appear among the animals that live in industrial areas. As soot from factory smoke darkens the landscape, the frequency of melanic offspring in- creases until the original lighter forms become a mi- nority. The pigments involved are melanins (q.v.), and the species undergoing melanism rely on crypsis (q.v.) to avoid being eaten. The most famous exam- ple of industrial melanism involves the moth Biston betularia (q.v.). See Appendix C, 1891, Tutt; 1958, Kettlewell; Bibliography, 2003, Hooper.

Indy a gene in Drosophila that has a profound ef- fect upon life span. The gene symbol is an acronym for I’m not dead yet. The gene encodes a protein, localized in the plasma membranes of cells of the fat body (q.v.), that transports molecules generated during the citric acid cycle (q.v.). Flies with two nor- mal alleles have a mean life span of 37 days. Flies heterozygous for Indy mutants have a mean life span of 70 days. Indy homozygotes show only a 15% in- crease in life span. See heterozygote advantage. inelastic collision See collision. infectious nucleic acid purified viral nucleic acid capable of infecting a host cell and causing the sub- sequent production of viral progeny. infectious transfer the rapid spread of extrachro- mosomal episomes (plus any integrated chromo- somal genes) from donor to recipient cells in a bacte- rial population. inflorescence 1. a flower cluster. 2. the arrange- ment and mode of development of the flowers on a floral axis.

See determinant inflorescence, indetermi- nant inflorescence. influenza viruses viruses that belong to the Or- thomyxoviridae and cause epidemics of influenza in humans, pigs, horses, and birds. The last great epi- demic occurred during the first world war. Between 1918 and 1919 there were 50 million deaths world- wide from influenza. The genome consists of eight molecules of linear negative-sense ssRNA, which form a helical complex with a protein called NP.

Several other proteins form spikes and mushroom- shaped projections that radiate from the outer sur- face of the viral envelope. These viruses undergo fre- quent changes in their antigenic properties as a re- sult of small mutational changes. See enveloped viruses, virus, zoonotic viruses. informed consent the permission given by an indi- vidual that allows a previously discussed procedure to be performed in the future. Amniocentesis (q.v.) would be an example of such a procedure.

It is known that the individual has been made aware of the risks and benefits of the procedure and the im- plications of the findings. See genetic counseling. in-frame mutation a mutation, generally of the missense type, that does not cause a reading frame shift (q.v.). inheritance of acquired characteristics See ac- quired characteristics, Lamarckism. initiation codon See start codon. initiation factors proteins required for the initia- tion of protein synthesis. One (protein IF3) is re- quired for the binding of the 30S particle to mRNA. A second (protein IFI) binds to f-met-tRNA and helps it attach to the 30S mRNA initiation complex. A third protein (IF2) is required, although its precise function is unclear. Initiation factors are symbolized IF in prokaryotes and elF in eukaryotes, followed by a number. See N-formylmethionine, scanning hy- pothesis, translation.

In situ hybridization

initiator a molecule that initiates replication once it binds to a replicator. See replicon. initiator tRNA the special tRNA molecule which provides the amino acid that starts the protein chain. In the case of prokaryotes, the initiator tRNA carries N-formylmethionine, while eukaryotic initiators carry methionine. See transfer RNA. innate immunity an immunse response activated by receptors that recognize foreign molecules, such as lipopolysaccharides (q.v.), attached to the sur- faces of common microorganisms. Drosophila com- bats microbial infections by having receptors of this sort.

Activation of the receptors induces cells of the fat body (q.v.) to synthesize antimicrobial peptides. DNA chip (q.v.) technologies have been used to identify over 400 genes in Drosophila that play roles in innate immunity. Drosophila immune-competent cells can express more than 18,000 isoforms contain- ing immunoglobulin receptor domains by alternative splicing (q.v.) of the Dscam gene. Contrast with adaptive immunity. inner cell mass (ICM) in mammals, a clump of embryonic cells that attaches itself to the inside of the trophoblast (q.v.) during blastocyst (q.v.) forma- tion and from which the fetus (q.v.) develops.

The ICM is one of the sources of embryonic stem cells (q.v.). innervation the nerve supply to a particular organ. inoculum a suspension of cells introduced into a nutrient medium to start a new culture. input load See genetic load. inosine hypoxanthine riboside. See rare bases. inquiline an animal that lives in the abode of an- other species. insect ovary types three types of ovaries are found among insects. The panoistic ovary appears to be the ancestral type.

Here, all oogonia (except stemline oogonia) are eventually transformed to oocytes. In meroistic ovaries, both oocytes and nurse cells (q.v.) are generated. These may be organized within the ovariole in two ways. In the polytrophic meroistic ovary, the nurse cells and oocytes alternate along the length of the ovariole.

In the telotrophic meroistic ovary, the nurse cells are restricted to the germarium and are connected to oocytes in early stages of their development by cytoplasmic processes called nutri- tive chords. Panoistic ovaries are found in insects be- longing to the more primitive orders (Archeognatha, Zygentoma, Ephemeroptera, Odonata, Plecoptera, Phasmida, Orthoptera, and Dictyoptera). Polytro- phic meroistic ovaries occur in the Psocoptera, Phthiraptera, Hymenoptera, Trichoptera, Lepidop- tera, and Diptera. Telotrophic ovaries occur in the Hemiptera, Coleoptera, Raphidioptera, and Mega- loptera. insertion the addition of one or more base pairs into a DNA molecule; a type of mutation commonly induced by acridine dyes or by mobile insertion se- quences (q.v.).

See indels. insertional inactivation abolition of the func- tional properties of a gene product by insertion of a foreign DNA sequence into that gene’s coding se- quence; used in genetic engineering as a means of detecting when a foreign DNA sequence has be- come integrated into a plasmid or other recipient molecule of interest. insertional mutagenesis alteration of a gene as a consequence of inserting unusual nucleotide se- quences from such sources as transposons, viruses, transfection, or injection of DNA into fertilized eggs. Such mutations may partially or totally inacti- vate the gene product or may lead to altered levels of protein synthesis. See insertional inactivation, in- sertion sequences, transgenic animals.

insertional translocation See translocation. insertion sequences transposable elements (q.v.) first detected as the cause of spontaneous mutations in E. coli. The majority of IS elements studied so far range in size from 0.7 to 1.8 kilobase pairs. IS ter- mini carry inverted repeats of about 10 to 40 base pairs, which are believed to serve as recognition se- quences for a transposase (q.v.). The IS also contains a gene that encodes the transposase.

The genome of the E. coli strain sequenced in 1997 contained 10 dif- ferent insertion sequences, and most of these were present at multiple sites along the chromosome. See Appendix C, 1969, Shapiro; 1997, Blattner et al. insertion vector See lambda cloning vehicle. in silico a term that refers to inferred relationships and hypotheses that are generated from the analysis of information retrieved from computer-based data banks that contain amino acid or nucleotide se- quences. The information analyzed resides in silicon chips, hence the use of silico in the term. in situ “in place”; in the natural or original posi- tion. in situ hybridization a technique utilized to local- ize, within intact chromosomes, eukaryotic cells, or bacterial cells, nucleic acid segments complementary to specific labeled probes. To localize specific DNA

sequences, specimens are treated so as to denature DNAs and to remove adhering RNAs and proteins. The DNA segments of interest are then detected via hybridization with labeled nucleic acid probes. The distribution of specific RNAs within intact cells or chromosomes can be localized by hybridization of squashed or sectioned specimens with an appro- priate RNA or DNA probe. See Appendix C, 1969, Gall and Pardue; 1975, Grunstein and Hogness; 1981, Harper and Saunders; 1983, Hafen, Levine, and Gehring; chromosome painting, fluorescence in situ hybridization (FISH). instar the period between insect molts. instinct an unlearned pattern of behavior.

instructive theory an early immunological theory in which it was believed that the specificity of anti- body for antigen was conferred upon it by its initial contact with the antigen. This theory has been dis- carded in favor of the clonal selection theory (q.v.), in which specificity exists prior to contact with an- tigen. insulator DNAs segments of DNA that serve to isolate neighboring genes within a specific domain by blocking interactions between enhancers (q.v.) on one side of a domain from the inappropriate target promotors of neighboring genes belonging within an adjacent domain.

Specific proteins that bind to insu- lator DNA segments are responsible for defining cer- tain chromosomal regions, such as the interbands and puff boundaries in polytene chromosomes. See Appendix C, 1995, Zhao, Hart, and Laemmli; 2000, Bell and Felsenfeld; H19, matrix attachment regions, parental imprinting. insulin a polypeptide hormone produced by the beta cells in the islets of Langerhans (q.v.). Insulin causes a fall in the sugar concentration of the blood, and its deficiency produces the symptoms of diabe- tes mellitus. Beef insulin was the first protein to have its amino acid sequence determined.

This molecule (illustrated below) is made up of an A polypeptide (21 amino acids long) and a B peptide (containing 30 amino acids) joined by two disulfide bridges. Sanger’s analysis showed that proteins had chemical structures in the form of specific sequences of amino acids. In humans, insulin is encoded by a gene on the short arm of chromosome 11 at band 15.5. A genetically engineered form of human insulin goes under the trade name humulin (q.v.).

See Appendix C, 1921, Banting and Best; 1955, Sanger et al.; 1964, Hodgkin; 1977, Gilbert; 1982, Eli Lilly; diabetes mellitus, proinsulin. insulin-like growth factors 1 and 2 (IGF-1 and IGF-2) single-chain protein growth factors that closely resemble insulin and each other in their amino acid sequences. Both IGF-1 and IGF-2 and their receptors are present as early as the eight-cell stage in the mouse, and growth is retarded if either igf-1 or igf-2 gene is inactivated. IGF-2 is essential for early embryonic growth in the mouse, but IGF- 1 seems more important in the later development. The IGF-2 gene shows parental imprinting (q.v.).

In Caenorhabditis the gene for the IGF-1 receptor is en- coded by daf-2, and mutations of this gene cause a two- to threefold increase in the worm’s normal (10- day) life span. See H9. integrase an enzyme that catalyzes a site-specific recombination (q.v.) by which a prophage becomes integrated into or excised (deintegrated) from a bac- terial chromosome; an excisionase enzyme is also re- quired for the excision process. See lambda (λ) bacte- riophage.

The term also refers to a family of site- specific recombinases. See site-specific recombinase. integral protein an amphipathic (q.v.) protein that is firmly embedded in the plasma membrane. Integral proteins interact with both the hydrophobic (q.v.) and the hydrophilic (q.v.) components of the phospholipid bilayer and are difficult to isolate. Compare with peripheral protein. See aquaporins, cal- nexin, lipid bilayer model.

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