The Organization and Diversity of Immunoglobulin Genes

Leder, Philip; Honjo, Tasuku; Packman, Seymour; Swan, David C.; Nau, Marion M.; Norman, Barbara

doi:10.1073/pnas.71.12.5109

Cited by 39 publications

(23 citation statements)

References 16 publications

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“…Their argument has been supported by the finding that there are few copies of light chain constant-region genes (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) and, more recently, by evidence derived directly from cloned immunoglobulin gene fragments (15,16). It has further been suggested that variable-and constant-region gene sequences are rearranged during the somatic differentiation of immunocytes so as to bring constant-and variable-region genes together (17,18).…”

mentioning

confidence: 54%

Multiple related immunoglobulin variable-region genes identified by cloning and sequence analysis.

Seidman¹,

Leder²,

Edgell³

et al. 1978

Proc. Natl. Acad. Sci. U.S.A.

114

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We have identified at least six EcoRI fragments of mouse DNA that encode variable-region gene sequences closely related to the mouse X light chain, MOPC-149. Two of these fragments have been cloned, and the entire nucleotide sequence of the variable-region genes encoded on each has been determined. Both genes encode closely related variable-region sequences extending from codon position 1 through position 97. Neither fragment encodes a constant-regon sequence. Although both genes are closely related, they differ from one another and from the sequence expressed in the MOPC-149 cell from which they were cloned. These few differences cluster within the complementarity-determining regions although several occur in framework sequences as well. We therefore conclude that an antibody-producing cell contains genetic information corresponding to its expressed sequence and several other closely related but silent sequences. These initial results raise the possibility that similar sets of genes might exist corresponding to each of the many subgoups already identified among mouse X light chains. If true, this would further suggest that the mouse genome might be rich enough in variable-region genes so as to encode a major portion of the variable-region repertoire.The unique pattern of antibody structure led Dreyer and Bennett (1) to propose that the constant and variable regions of the immunoglobulin light chain are encoded separately in chromosomal DNA. Their argument has been supported by the finding that there are few copies of light chain constant-region genes (2-14) and, more recently, by evidence derived directly from cloned immunoglobulin gene fragments (15,16). It has further been suggested that variable-and constant-region gene sequences are rearranged during the somatic differentiation of immunocytes so as to bring constant-and variable-region genes together (17,18). The question of whether this rearrangement of genes is essential for their expression remains unanswered. Also unanswered is the important question of how the diversity represented in immunoglobin variable regions is produced-through evolutionary or somatic mechanisms or a combination of both. Several useful models that define contending germ-line and somatic mutation hypotheses have been advanced to explain this interesting genetic phenomenon (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31).In order to begin to distinguish between these models (the germ-line model requires many variable region genes; the somatic model, few), we have cloned (32) two closely related K variable-region genes derived from the mouse plasmacytoma, MOPC-149. We have determined the entire nucleotide sequence of the coding segments and portions of the flanking sequences of both these genes and compared them to one another and to a cloned cDNA sequence corresponding to a variable-region gene expressed in this cell line. Among other inferences we may draw from the structure of these genes, the identification of three closely related genetic sequences in a committed, ...

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mentioning

confidence: 54%

Multiple related immunoglobulin variable-region genes identified by cloning and sequence analysis.

Seidman¹,

Leder²,

Edgell³

et al. 1978

Proc. Natl. Acad. Sci. U.S.A.

114

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“…1º Tanto em camundongos (LEDER et al, 1974) quanto em plantas, cerca de 1% do genoma está comprometido com a elaboração de proteínas que protegem de forma específica seus hospedeiros contra patógenos: imunoglobulinas nos vertebrados, e PRs nas plantas.…”

Section: Resposta Integrada De Defesa Da Planta Contra a Infecção Do unclassified

Imunidade inata e específica em plantas

Menezes¹

2009

Semin. Cienc. Biol. Saude

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ResumoPlantas e animais são capazes de reconhecer e distinguir entre estruturas moleculares próprias e não-próprias. Estudos recentes nas relações hospedeiro-parasitas têm exposto mecanismos comuns e contrastantes de resistência do hospedeiro tanto em animais como em plantas. Algumas estruturas e estratégias de defesa filogeneticamente antigas têm sido mantidas por desenvolvimento paralelo, enquanto várias outras emergiram mais recentemente durante a filogênese. Embora desprovidas de moléculas de imunoglobulina, células circulantes e processo de fagocitose, as plantas utilizam com sucesso várias defesas físicas e químicas pré-formadas, bem como induzem estratégias de imunidade adaptativa. Esta revisão apresenta a evolução recente nos estudo de aspectos de imunidade comparada, presentes em animais e as plantas. Palavras-chave: Imunidade em plantas. Imunidade comparada. Resistência sistêmica adquirida. AbstractPlants and animals are able to recognize and distinguish between self and non-self molecular structures. Recent studies concerning host-parasite relations have presented the common and contrasting mechanisms of host resistance in both plants and animals. Some phylogenetically old defense structures and strategies have been maintained by means of parallel development, while several others have emerged more recently during phylogenesis. Although lacking immunoglobulin molecules, circulating cells and phagocytosis process, plants successfully use several pre-established physical and chemical defenses as well as induce adaptive-immune response strategies. This review presents recent developments in the study of comparative immunity aspects that are present in animals and plants.

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“…From RNA-DNA hybridization studies, only a few copies of a particular C region seem to be present in the genome (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). The number of V region genes present in the germ line is still not resolved.…”

Section: Abstracimentioning

confidence: 99%

Organization of kappa light chain genes in germ-line and somatic tissue.

Joho¹,

Weissman²,

Early³

et al. 1980

Proc. Natl. Acad. Sci. U.S.A.

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ABSTRACIWe studied the organization of the K light chain genes in germ-line (sperm) and somatic (embryo) tissues. We constructed a plasmid containing a DNA insert coding for the K chain MOPC 167 and used the Southern blotting technique to determine the organization of K variable and constant region genes. In the haploid genome of the mouse there is only one constant region gene detectable and it has the same organization in sperm and embryo DNAs. There are several variable region genes in sperm and embryo that are related to the Vk167 gene. The organization of the V genes in sperm and embryo DNAs is identical. These results show that there is no rearrangement of variable region genes (or "minigenes") during early embryogenesis.The polypeptides that form antibody molecules can be divided into two-distinct parts, the variable (V) and the constant (C) region. From RNA-DNA hybridization studies, only a few copies of a particular C region seem to be present in the genome (1-11). The number of V region genes present in the germ line is still not resolved. Because the V regions determine the antibody specificity, the question of the origin of antibody diversity is an integral part of the number and organization of the V region genes. Several hypotheses have been proposed to explain the origin of antibody diversity. The strict germ-line hypothesis proposes that there are multiple V region genes and each antibody-producing cell chooses to express only one of these genes from the inherited V region repertoire (12). The various somatic diversification hypotheses explain the origin of antibody diversity quite differently. It is assumed that the germ line contains only a few V region genes and these are somatically diversified during ontogeny in order to yield many different V regions. A strict mutation hypothesis proposes that mutations (simple base changes) occur during differentiation of precursor cells into antibody-producing cells (13,14). These mutations may occur in the hypervariable part of the V region or they may occur randomly throughout the V region gene. The somatic recombination hypothesis postulates a limited number of V genes in the germ line which undergo unequal crossing-over during ontogeny to form recombined V genes, thereby expanding the V region information that is expressed (15, 16).Wu and Kabat (17) pointed out that amino acid sequence analysis of several hundred light chain V regions suggested a division of V regions into four "framework" regions with very little variability (FR1, FR2, FR3, and FR4) and three hypervariable regions (HV1, HV2, and HV3) that exhibit extensive sequence diversity. Kabat and others later proposed that each of these V region segments was a germ-line minigene that was inherited independently (18)(19)(20). By these hypotheses, subgenicThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact. 1106 elements representing all po...

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The Organization and Diversity of Immunoglobulin Genes

Cited by 39 publications

References 16 publications

Multiple related immunoglobulin variable-region genes identified by cloning and sequence analysis.

Multiple related immunoglobulin variable-region genes identified by cloning and sequence analysis.

Imunidade inata e específica em plantas

Organization of kappa light chain genes in germ-line and somatic tissue.

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