Mapping of Heavy Chain Genes for Mouse Immunoglobulins M and D

Liu, CP; Tucker, P W; Mushinski, J. Frederic; Blattner, F. R.

doi:10.1126/science.6774414

Cited by 186 publications

(53 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Most important for this investigation, ␦ mRNA is highly enriched in IgM ϩ cells, again suggesting that Xenopus IgD is principally a TM receptor encoded by differentially spliced mRNA, as in mouse and human (25).…”

Section: Resultsmentioning

confidence: 99%

IgD, like IgM, is a primordial immunoglobulin class perpetuated in most jawed vertebrates

Ohta

Flajnik²

2006

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

197

138

View full text Add to dashboard Cite

IgD has remained a mysterious Ig class and a bane to immunology students since its discovery >40 years ago. Its spotty occurrence in mammals and birds and the discovery of an isotype with similarities to IgD in bony fish are perplexing. We have identified IgD heavy (H) chain (␦) from the amphibian Xenopus tropicalis during examination of the IgH locus. The Xenopus ␦ gene is in the same position, immediately 3 of the IgM gene, as in mammals, and it is expressed only in the spleen at low levels, primarily as a transmembrane receptor by surface IgM ؉ cells. Our data suggest that frog IgD is expressed on mature B cells, like in mouse͞human. Unexpectedly, Xenopus IgD is orthologous to IgW, an Ig isotype found only in cartilaginous fish and lungfish, demonstrating that IgD͞W, like IgM, was present in the ancestor of all living jawed vertebrates. In striking contrast to IgM, IgD͞W is evolutionarily labile, showing many duplications͞deletions of domains, the presence of multiple splice forms, existence as predominantly a secretory or transmembrane form, or loss of the entire gene in a species-specific manner. Our study suggests that IgD͞W has played varied roles in different vertebrate taxa since the inception of the adaptive immune system, and it may have been preserved as a flexible locus over evolutionary time to complement steadfast IgM.evolution ͉ immune system S ince the pioneering work of comparative immunologists in the 1960s, IgM has been the Ig isotype believed to be primordial and most stable in vertebrate evolution (1). Despite differences in the degree of polymerization of the secretory form in different vertebrate groups (1, 2) and a major splice variant of the transmembrane (TM) form in teleost fish (3), IgM is renowned for its molecular, biochemical, and functional stability. Present in all living jawed vertebrates, IgM is the first isotype to be expressed both in ontogeny and during humoral adaptive immune responses and is found as the major TM receptor on the surface of both conventional and ''innate'' B cells (4).By contrast, IgD has remained an enigmatic isotype since its discovery long ago (5). Like IgM, IgD is expressed as a TM receptor on B cells of mouse and human, generated as a result of alternative splicing of pre-mRNA containing the transcribed variable (V) region and the IgM and IgD heavy (H) chain constant (C) regions ( and ␦, respectively). Because of its spotty presence in mammals and absence in birds, IgD was assumed to be a recently evolved isotype (6). However, the discovery of an isotype in ray-finned bony fish with sequence similarity to IgD (7) and its presence in some mammals previously believed to lack IgD (8) have greatly modified our view of Ig isotype evolution and suggested it may have arisen much earlier.A similarly strange phylogenetic jump surrounds the isotype IgW, which was discovered first in skates (9, 10) and later in sharks (11,12). The secreted version of the IgW H chain ( ) is present in long and short forms in all elasmobranchs tested to date, and the TM form is al...

show abstract

Section: Resultsmentioning

confidence: 99%

IgD, like IgM, is a primordial immunoglobulin class perpetuated in most jawed vertebrates

Ohta

Flajnik²

2006

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

197

138

View full text Add to dashboard Cite

show abstract

“…However, posttranscriptional regulation of 8 polypeptide synthesis appears to differ for the two differentiative stages. Activated B cells synthesize decreased levels of 8 polypeptides due to lower mRNA abundance, while neonatal lymphocytes are less efficient in their ability to process nascent 8 polypeptide chains.…”

mentioning

confidence: 99%

Regulation of immunoglobulin D synthesis in murine neonatal B lymphocytes.

Yuan¹

1986

Mol. Cell. Biol.

View full text Add to dashboard Cite

We analyzed the regulatory basis for the lower expression of immunoglobulin D (IgD) in lymphocytes from neonatal mice of various ages. The results indicate that the relative transcriptional rate of RNA for 8 chains is similar to adult levels even in cells which have not started to express IgD. These results suggest that very early after the initiation of > gene transcription, a defined fraction of polymerases is programmed to progress through the termination site to the 8 exons regardless of the developmental stage of the cell. Similar results were obtained from adult CBA/N mice whose spleens contain a large fraction of cells expressing low levels of TgD. On the other hand, the relative steady state level of mRNA in neonatal lymphocytes is approximately half of that in adults, suggesting that there may be differences'in the processing or stability of the nascent transcript. In addition, measurements of the in vivo translation rate show that an inefficient 8 polypeptide chain processing machinery in neonatal lymphocytes is also an important factor contributing to the reduced expression of IgD.

show abstract

“…These cells are useful for examining specific B cell characteristics and biosynthetic patterns because large quantities of a relatively pure population of cells can be obtained. While extrapolations to normal cells must be done with great care, the use of LBL and cell lines derived from B cell malignancies has permitted the generation of a large amount of data on the biochemical properties of the different species of/~ heavy chains (10,19,20) and on the DNA sequences encoding the # chain gene (21)(22)(23). However, very little information exists at the molecular level about the mechanisms controlling the synthesis of the various types of# heavy chain molecules during differentiation.…”

mentioning

confidence: 99%

Differential regulation of membrane and secretory mu chain synthesis in human beta cell lines. Regulation of membrane mu or secreted mu.

Hendershot¹,

Levitt²

1982

The Journal of Experimental Medicine

View full text Add to dashboard Cite

Regulation of membrane and secretory mu synthesis was examined in human lymphoblastoid cell lines representing various stages of differentiation. Immunoglobulin phenotype was determined by surface and cytoplasmic staining with fluorochrome-conjugated antibodies and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis of anti-mu precipitable cellular products. The thymidine analogue, 5-bromo-2'-deoxyuridine (BUdR), which inhibits differentiation-specific proteins in a variety of systems, was used to examine regulation of immunoglobulin synthesis. We found that BUdR had a differential effect on membrane (mum) and secretory (mus) type mu heavy chains. Ig production in pre-B and plasma cell-like lines, which make mus, was unaffected by BUdR. However, surface expression of IgM (mum) in B cell lines was drastically inhibited at similar doses of BUdR without diminishing total Ig or protein synthesis. Examination of labeled mu chains from control and BUdR-treated B cell lines by SDS-PAGE revealed the production of two sizes of mu (mum and mus) in control cells and only the smaller size (mus) in BUdR-treated cells. This size difference could not be attributed to alterations in glycosylation of the molecules. These data show that BUdR inhibits the production of membrane mu chains without diminishing secretory mu chain synthesis in the same cell. Our findings suggest that thymidine-rich regions of the genome are involved in the regulation of mum vs. mus during B cell differentiation.

show abstract

Mapping of Heavy Chain Genes for Mouse Immunoglobulins M and D

Cited by 186 publications

References 33 publications

IgD, like IgM, is a primordial immunoglobulin class perpetuated in most jawed vertebrates

IgD, like IgM, is a primordial immunoglobulin class perpetuated in most jawed vertebrates

Regulation of immunoglobulin D synthesis in murine neonatal B lymphocytes.

Differential regulation of membrane and secretory mu chain synthesis in human beta cell lines. Regulation of membrane mu or secreted mu.

Contact Info

Product

Resources

About