Biomaterial Database

Structure and function of immunoglobulin genes and immunoglobulin precursors. 1976

I Schechter, and Y Burstein, and S Spiegelman

To gain information on the origin of antibody diversity (somatic mutation or germ line hypothesis) it is necessary to determine the number of V region genes. For this purpose the capacity of a distinct V region probe to hybridize and quantify V genes of the same and different subgroups should be established. Relevant information on this issue was obtained from the extent of cross-hybridization of a distinct L chain cDNA with mRNAs coding for L chains of the same and different subgroups. The results indicated that: (1) V regions of similar amino acid sequence are coded by similar nucleotide sequence (this is not self-evident because of the degeneracy of the genetic code); (2) the nucleic acid probe to one V region may anneal and quantify V genes of members of the same subgroup. Molecular hybridizations of the cDNA probe with nuclear DNA showed that: (1) the number of kappa type C genes is small (about 2 per haploid genome); (2) the number of V genes presumably is also small; (3) there is no amplification of these genes in myeloma cells that produce large amounts of the Ig. These results support the somatic mutation model for the generation of antibody diversity. New information on the structure and controlled expression of Ig genes was obtained from the study of L chain precursors, which are the immediate product of L chain mRNA translation in vitro. In the precursors extra peptide segments (19-22 residues in length) precede the N-terminus of the mature L chain. Amino acid sequence analyses of the precursors provide evidence that: (1) the gene coding for the V region is larger than hitherto known; (2) duplication of a short DNA segment occurred in the structural gene coding for the MOPC-321 precursor; (3) translation of the L chain mRNA may be contingent on the nucleotide sequence coding for the extra piece; (4) cleavage of the extra piece may regulate secretion of mature L chain; (5) the extra piece is remarkably hydrophobic, suggesting that the role of the extra piece is to anchor the precursor in cell membranes, in a manner similar to the function of the "hydrophobic domain" of membrane bound proteins. We propose that most precursor molecules are directed to the endoplasmic reticulum where the extra piece is cleaved to yield mature Ig destined for secretion; a few precursor molecules escape cleavage and are anchored by means of the hydrophobic extra piece in the cell-surface membrane to serve as the antigen-recognizing receptor.

UI	MeSH Term	Description	Entries
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
D007147	Immunoglobulin Light Chains	Polypeptide chains, consisting of 211 to 217 amino acid residues and having a molecular weight of approximately 22 kDa. There are two major types of light chains, kappa and lambda. Two Ig light chains and two Ig heavy chains (IMMUNOGLOBULIN HEAVY CHAINS) make one immunoglobulin molecule.	Ig Light Chains,Immunoglobulins, Light-Chain,Immunoglobulin Light Chain,Immunoglobulin Light-Chain,Light-Chain Immunoglobulins,Chains, Ig Light,Chains, Immunoglobulin Light,Immunoglobulins, Light Chain,Light Chain Immunoglobulins,Light Chain, Immunoglobulin,Light Chains, Ig,Light Chains, Immunoglobulin,Light-Chain, Immunoglobulin
D009194	Myeloma Proteins	Abnormal immunoglobulins characteristic of MULTIPLE MYELOMA.	M Components,Proteins, Myeloma
D009693	Nucleic Acid Hybridization	Widely used technique which exploits the ability of complementary sequences in single-stranded DNAs or RNAs to pair with each other to form a double helix. Hybridization can take place between two complimentary DNA sequences, between a single-stranded DNA and a complementary RNA, or between two RNA sequences. The technique is used to detect and isolate specific sequences, measure homology, or define other characteristics of one or both strands. (Kendrew, Encyclopedia of Molecular Biology, 1994, p503)	Genomic Hybridization,Acid Hybridization, Nucleic,Acid Hybridizations, Nucleic,Genomic Hybridizations,Hybridization, Genomic,Hybridization, Nucleic Acid,Hybridizations, Genomic,Hybridizations, Nucleic Acid,Nucleic Acid Hybridizations
D011498	Protein Precursors		Precursors, Protein
D004247	DNA	A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).	DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D005796	Genes	A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.	Cistron,Gene,Genetic Materials,Cistrons,Genetic Material,Material, Genetic,Materials, Genetic
D005815	Genetic Code	The meaning ascribed to the BASE SEQUENCE with respect to how it is translated into AMINO ACID SEQUENCE. The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (CODON).	Code, Genetic,Codes, Genetic,Genetic Codes
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia