Expression of IgD may use both DNA rearrangement and RNA splicing mechanisms

Moore, Kw.; Rogers, J. H.; Hunkapiller, Tim; Early, P.; Nottenburg, Carol; Weissman, Irving L.; Bazin, Hervé; Wall, Randolph; Le, Hood

doi:10.1073/pnas.78.3.1800

Cited by 134 publications

(59 citation statements)

References 40 publications

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“…The A2 line also has a VHDJH rearrangement at its other heavy-chain allele, but this rearrangement is nonfunctional due to an in-phase termination codon in the D segment (6). Because the A-2 line apparently contained two copies of the C, gene, we suggested that the switch to Y2b production in this line might have occurred, at least in part, by a differential RNA-processing mechanism (5) similar to that used for the simultaneous expression of ,u and 8 by B-lymphocytes (20,23,27 and mapped by digestion with various restriction enzymes as described previously (6). Various regions of the inserts were sequenced by the method of Maxam and Gilbert (26) as previously described (6).…”

Section: 42mentioning

confidence: 98%

Molecular basis of heavy-chain class switching and switch region deletion in an Abelson virus-transformed cell line.

DePinho¹,

Kruger²,

Andrews³

et al. 1984

Mol. Cell. Biol.

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We demonstrated that a subclone of an Abelson murine leukemia virus-transformed B-lymphoid cell line switched from I. to '2b expression in vitro, by the classical recombination-deletion mechanism. In this line, the expressed VHDJH region and the Cy2b constant region gene were juxtaposed by a recombination event which linked the highly repetitive portions of the S,, and Sy2b regions and resulted in the loss of the C, gene from the intervening region. An additional recombination event in this subclone involved an internal deletion in the S,J region of the expressed (switched) allele. One end of this deletion occurred very close to the switch recombination point. Despite the recombination-deletion mechanism of switching, the y2b-producing line retained two copies of the C, gene and two copies of the sequence just 5' to the Sy2b recombination point. The possible significance of the retention of these sequences to the mechanism of class switching is discussed.

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Section: 42mentioning

confidence: 98%

Molecular basis of heavy-chain class switching and switch region deletion in an Abelson virus-transformed cell line.

DePinho¹,

Kruger²,

Andrews³

et al. 1984

Mol. Cell. Biol.

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“…Our approaches to immunology and biology were quite complementary, and I later took a sabbatical with Lee in 1981 to learn how to work with genes myself. He had some great students and fellows at the time, e.g., Mark Davis, Mike Hunkapiller, Michael Steinmetz, Phil Early, and Stuart Kim, and we began a series of collaborations where my lab would isolate pure normal cell subsets and together we would examine the germline or rearranged status of immunoglobulin genes (73,74) and then TCR genes (75). We continue to collaborate to this day.…”

Section: The Thymus Thymic Maturation B Lymphocyte Development Hommentioning

confidence: 99%

How One Thing Led to Another

Weissman

2016

Annu. Rev. Immunol.

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I started research in high school, experimenting on immunological tolerance to transplantation antigens. This led to studies of the thymus as the site of maturation of T cells, which led to the discovery, isolation, and clinical transplantation of purified hematopoietic stem cells (HSCs). The induction of immune tolerance with HSCs has led to isolation of other tissue-specific stem cells for regenerative medicine. Our studies of circulating competing germline stem cells in colonial protochordates led us to document competing HSCs. In human acute myelogenous leukemia we showed that all preleukemic mutations occur in HSCs, and determined their order; the final mutations occur in a multipotent progenitor derived from the preleukemic HSC clone. With these, we discovered that CD47 is an upregulated gene in all human cancers and is a “don't eat me” signal; blocking it with antibodies leads to cancer cell phagocytosis. CD47 is the first known gene common to all cancers and is a target for cancer immunotherapy.

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“…Other probes used in cosmid characterization included a 3.7-kb Sac I fragment encompassing the switch (S) region S, and a 4.5-kb BamHI fragment encompassing the CM and membrane ,u region of plasmid pSV-Vul (18); a 0.8-kb EcoRI-HindIII fragment from plasmid pSy3 encompassing the switch Sy3 region (23); a 8-kb EcoRI fragment of plasmid pSp51, a subclone of CHSp~u7 (24), encompassing the CB region; and a 0.9-kb and a 0.4-kb Pst I fragment of plasmid C230 encompassing CE (25).…”

Section: Methodsmentioning

confidence: 99%

Immunoglobulin heavy chain locus of the rat: striking homology to mouse antibody genes.

Brüggemann¹,

Free²,

Diamond³

et al. 1986

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

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DNA encoding the rat diversity segment (D), joining segment (JH), and constant (C) region mu, gamma 2a, gamma 1, gamma 2b, epsilon and alpha of the Ig heavy chain has been isolated from a cosmid library. Restriction mapping allowed us to identify two gene clusters: D-JH-C mu and C gamma 1-C gamma 2b-C epsilon-C alpha in addition to a single C gamma 2a gene. Analysis of genomic DNA by Southern blotting permitted identification of the C gamma 2c gene and led to the proposal of the following gene order for the rat Ig heavy chain locus: D-JH-C mu-C delta-(C gamma 2c, C gamma 2a)-C gamma 1-C gamma 2b-C epsilon-C alpha. There is striking homology between the rat and mouse Ig heavy chain loci as regards gene order and distance between CH genes. Partial DNA sequencing confirms this homology and shows that exon sequences are more conserved than are intron sequences. One of the most conserved intron regions between rat and mouse is that spanning the Ig heavy chain enhancer (91% homology). However, the relationship between the different C gamma subclasses in rat differs from that in mouse. Comparison of the C gamma CH3 domains shows that the rat C gamma 2b gene is most homologous to mouse C gamma 2a/b, whereas the rat C gamma 1 and C gamma 2a genes, both very similar to each other, are most homologous to the mouse C gamma 1 gene.

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Expression of IgD may use both DNA rearrangement and RNA splicing mechanisms

Cited by 134 publications

References 40 publications

Molecular basis of heavy-chain class switching and switch region deletion in an Abelson virus-transformed cell line.

Molecular basis of heavy-chain class switching and switch region deletion in an Abelson virus-transformed cell line.

How One Thing Led to Another

Immunoglobulin heavy chain locus of the rat: striking homology to mouse antibody genes.

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