Synthesis of Multiple Immunoglobulin Classes by Single Lymphocytes

Pernis, Benvenuto; Forni, Luciana; Luzzati, Alma L.

doi:10.1101/sqb.1977.041.01.023

Cited by 93 publications

(28 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The S region derives its name from its putative function in the somatic chromosome rearrangements involved in the "heavy chain switch." This phenomenon involves a transition from production of IgM to that of IgG, IgE, or IgA during the life of a B lymphocyte without changing the antigen specificity of the molecule (6,7). This is believed to be the result of DNA deletions removing the DNA segment between the heavy chain variable region gene and the constant region gene actually used for antibody production (8,9), after somatic recombination between the homologous S regions located 5' ofmost immunoglobulin genes.…”

mentioning

confidence: 99%

Multiple DNA fragment polymorphisms associated with immunoglobulin mu chain switch-like regions in man.

Migone¹,

Feder²,

Cann³

et al. 1983

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

View full text Add to dashboard Cite

DNA probes containing the switch region (S) associated with the human immunoglobulin heavy chain ,u gene were used to investigate polymorphisms in the germ-line human DNA. Six polymorphisms, detected by a single restriction enzyme (Sst I) are described. Linkage studies in 29 families show that five of the six polymorphisms, although relatively unassociated in random individuals, segregate in complete linkage one to the other and to Gm allotypes (markers on the heavy chain of IgG), while the sixth segregates independently. Altogether, when one considers the DNA markers at the five closely linked loci and the IgGI and IgG3 heavy chain allotypes, 33 different haplotypes have been described; of these, 28 are detected by the DNA polymorphism alone. Study of 158-187 random haplotypes showed strong linkage disequilibrium only between one DNA polymorphism (Sst A) and Gm. Of the polymorphic Sst I loci, one, SstE [associated with 2.2-to 2.7-kldobase (kb) fragments], is included in the As chain S region (S.,); another, Sst A (6.8-7.4 kb), must be very close to the yl-y3 chain gene cluster. Based on studies of an IgE human myeloma, a third polymorphism, Sst C (4.8-5.5 kb), should map 3' of the active e chain gene. An Sst I restriction enzyme map of phage clones carrying the two a chain genes indicates that Sst A and Sst C loci probably overlap with the cl and a2 S regions, respectively. Both deletion/duplications and point mutations were detected.Polymorphisms described in human immunoglobulin heavy chains are thus far limited to variation detected in protein antigenicity and sequence (1). Observations in mice indicate the existence of individual heterogeneity at the DNA germ-line level (2, 3). The possibilities offered by the study of individual variation at the DNA level by restriction enzyme analysis (4, 5) have prompted us to initiate a search for germ-line variation in the immunoglobulin heavy chain gene regions. We show that a single probe tested with a single enzyme can demonstrate polymorphisms at many loci. This is due to the fact that DNA sequences contained in the probe are repeated (with some variation) before several immunoglobulin heavy chain genes within the so-called "switch" (S) regions. The S region derives its name from its putative function in the somatic chromosome rearrangements involved in the "heavy chain switch." This phenomenon involves a transition from production of IgM to that of IgG, IgE, or IgA during the life of a B lymphocyte without changing the antigen specificity of the molecule (6, 7). This is believed to be the result of DNA deletions removing the DNA segment between the heavy chain variable region gene and the constant region gene actually used for antibody production (8, 9), after somatic recombination between the homologous S regions located 5' ofmost immunoglobulin genes. These S regions include multiple tandem repeats of sequences like G-A-G-C-T, G-G-G-G-T (10-14), and Y-A-G-G-T-T-C (15). The numerous polymorphisms we find allow us to analyze the genetic recombination in ...

show abstract

mentioning

confidence: 99%

Multiple DNA fragment polymorphisms associated with immunoglobulin mu chain switch-like regions in man.

Migone¹,

Feder²,

Cann³

et al. 1983

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

View full text Add to dashboard Cite

show abstract

“…One of the antibodies was anti-(31 or anti-(32, and the other antibody was either anti-CD3, which stains all mature T cells [18], anti-CD4 or anti-CD8; or anti-B220, which stains most cells of the B lineage [17], or anti-IgD, which stains the majority of mature, resting B cells [21]. All cell populations were also analyzed with a rat IgG2a antibody of irrelevant antigen specificity, as shown in Fig.…”

Section: General Remarksmentioning

confidence: 99%

Loss of the β1 subunit of the sodium pump during lymphocyte differentiation

1996

View full text Add to dashboard Cite

The Na,K-ATPase, or sodium pump, is responsible for maintaining cellular volume and is involved in receptor-mediated endocytosis; it is a ubiquitous transmembrane enzyme in higher eukaryotes and consists of an alpha and a beta subunit. In the mouse, two isotypes of beta with no known function have been identified: beta 1 and beta 2. We have studied the expression of beta 1 and beta 2 in lymphocytes from bone marrow, spleen, peripheral blood, and thymus. The beta 2 subunit is not expressed in any of the lymphocytes tested. Pre-B lymphocytes and the majority of mature, resting B cells in the bone marrow express the beta 1 subunit, as do all pre-T cells and mature thymocytes. In the spleen and in blood, beta 1 expression defines subsets of T and B lymphocytes. Mitogen-stimulated T and B cells lose beta 1 expression and do not express beta 2. While there is no indication that there is a change in alpha subunit isoform expression as a result of lymphocyte activation or that it is expressed in smaller amounts, there is a switch in the expression of the beta isoform.

show abstract

“…Whereas VK or VA genes are expressed only with the appropriate light chain C gene, a given heavy chain V gene can be expressed with more than one heavy chain C gene class. In addition, it appears that within a single lymphocyte there is the capacity to-switch the class ofC gene expressed while maintaining expression of the same V region (9)(10)(11). Recent studies from this laboratory (5,7) and others (8,12) have shown that this is accomplished by yet another type ofrecombination.…”

mentioning

confidence: 99%

Linkage of the four gamma subclass heavy chain genes.

Roeder¹,

Maki²,

Traunecker³

et al. 1981

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

View full text Add to dashboard Cite

The genes for the heavy-chain constant regions of the four y subclass immunoglobulins were identified in a set of overlapping mouse DNA fragments representing about 100 kilobase pairs (kb) ofthe mouse genome that was-cloned from bacteriophage A libraries ofBALB/c mouse embryo DNA. R-loop mapping studies show'that the genes are located 5'-Cy3-34 kb-Cy1-21 kbCV2b-15 kb-Cy2.-3' and lie in the same transcriptional orientation.Two DNA segments, one of 19 kb and another of 15 kb, that surround the CY2b and Cy2. genes, respectively, show considerable homology and implicate a tandem duplication mechanism in the evolution of this gene cluster.Immunoglobulins are composed oflight and heavy chains, each of which contains variable (V) and constant (C) portions. Genes encoding these proteins are created during differentiation by the somatic recombination between sequences flanking one of many V genes and those flanking a C gene. This process has been shown to occur with slight variations in each of the three independent immunoglobulin gene families-i.e., A (1, 2) and K (3, 4) light chain genes and heavy chain genes (5-8). However, heavy chain genes differ from light chain genes in an important aspect. Whereas VK or VA genes are expressed only with the appropriate light chain C gene, a given heavy chain V gene can be expressed with more than one heavy chain C gene class. In addition, it appears that within a single lymphocyte there is the capacity to-switch the class ofC gene expressed while maintaining expression of the same V region (9-11). Recent studies from this laboratory (5, 7) and others (8,12) Phylogenetic studies (14) indicate that all of the heavy chain C loci evolved from a common precursor gene. The various subclasses of Cy appeared recently-possibly after the divergence ofvarious species of mammals. Protein sequencing studies suggest that mouse IgG, and all human subclasses have a common ancestor (15) which differs from that of the human IgG2 subclasses. Whereas mouse Cy, and Cy2 genes may have diverged prior to the divergence ofspecies, the C y2, and Cy2b genes must have arisen as the result ofa very recent event. Comparisons of nucleotide sequences of these genes show substantial. conservation ofsequences, even in codon selection (16). Whereas protein and nucleotide sequence studies indicate that these genes share strong homologies, genetic studies indicate that the Cy genes are closely linked. No recombination between these genes has been detected in several thousand crosses (17).In this paper, we describe the arrangement of the four Cy subclass genes within a 100-kilobase pair (kb) segment ofmouse DNA. Analysis ofa set ofoverlapping recombinant phage clones has made it possible to determine the linkage arrangement and transcriptional orientation of these genes. In addition, strong flanking sequence homologies between Cy2b and Cyi genes suggest that a direct, tandem duplication ofa large block ofDNA created these two Cy genes from a common precursor. Preparation of Mouse Embryo Libraries. Bacteriopha...

show abstract

Synthesis of Multiple Immunoglobulin Classes by Single Lymphocytes

Cited by 93 publications

References 14 publications

Multiple DNA fragment polymorphisms associated with immunoglobulin mu chain switch-like regions in man.

Multiple DNA fragment polymorphisms associated with immunoglobulin mu chain switch-like regions in man.

Loss of the β1 subunit of the sodium pump during lymphocyte differentiation

Linkage of the four gamma subclass heavy chain genes.

Contact Info

Product

Resources

About