Stochastic rearrangement of immunoglobulin variable-region genes in chicken B-cell development.

Benatar, Tania; Tkalec, Lydia; Ratcliffe, Michael J. H.

doi:10.1073/pnas.89.16.7615

Cited by 52 publications

(36 citation statements)

References 33 publications

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“…5B). Thus, while essentially all VJ L junctions isolated from control IgM ϩ bursal B cells were in frame, consistent with results obtained elsewhere (19,20), only 48% of VJ L junctions isolated from mCD8␣ ϩ /IgM Ϫ bursal B cells were in frame. Taken together with the low frequency of V H and V L rearrangement, these results obviate the possibility that mCD8␣ ϩ /IgM Ϫ cells have been selected on the basis of endogenous sIgM expression.…”

Section: The Cytoplasmic Domain Of Ig␤ Is Not Sufficient To Support Bsupporting

confidence: 79%

“…In the chicken, by contrast, a single wave of Ig gene rearrangement occurs during embryogenesis during which V H and V L genes undergo rearrangement simultaneously (20,21). Allelic exclusion of chicken V gene rearrangement is not regulated by the products of rearrangement (55).…”

Section: Discussionmentioning

confidence: 99%

“…Only those B cell precursors that have undergone productive Ig gene rearrangement and can therefore express an intact BcR complex are selected for expansion in the bursa (19). Because rearrangement of chicken Ig (chIg) V H and V L genes occurs stochastically (20,21), there is no apparent role for the expression of a pre-BcR in chicken B cell development, and chicken homologues to VpreB and 5 have not been identified. Nonetheless, rearrangement of chIg genes generates a BcR of very limited diversity, which could be considered structurally analogous to the murine pre-BcR.…”

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confidence: 99%

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The Cytoplasmic Domain of Igα Is Necessary and Sufficient to Support Efficient Early B Cell Development

Pike

Iacampo

Friedmann

et al. 2004

The Journal of Immunology

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The B cell receptor complex (BcR) is essential for normal B lymphocyte function, and surface BcR expression is a crucial checkpoint in B cell development. However, functional requirements for chains of the BcR during development remain controversial. We have used retroviral gene transfer to introduce components of the BcR into chicken B cell precursors during embryonic development. A chimeric heterodimer, in which the cytoplasmic domains of chicken Igα and Igβ are expressed by fusion with the extracellular and transmembrane domains of murine CD8α and CD8β, respectively, targeted the cytoplasmic domains of the BcR to the cell surface in the absence of extracellular BcR domains. Expression of this chimeric heterodimer supported all early stages of embryo B cell development: bursal colonization, clonal expansion, and induction of repertoire diversification by gene conversion. Expression of the cytoplasmic domain of Igα, in the absence of the cytoplasmic domain of Igβ, was not only necessary, but sufficient to support B cell development as efficiently as the endogenous BcR. In contrast, expression of the cytoplasmic domain of Igβ in the absence of the cytoplasmic domain of Igα failed to support B cell development. The ability of the cytoplasmic domain of Igα to support early B cell development required a functional Igα immunoreceptor tyrosine-based activation motif. These results support a model in which expression of surface IgM following productive V(D)J recombination in developing B cell precursors serves to chaperone the cytoplasmic domain of Igα to the B cell surface, thereby initiating subsequent stages of development.

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Section: The Cytoplasmic Domain Of Ig␤ Is Not Sufficient To Support Bsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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The Cytoplasmic Domain of Igα Is Necessary and Sufficient to Support Efficient Early B Cell Development

Pike

Iacampo

Friedmann

et al. 2004

The Journal of Immunology

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“…All amplification reactions also contained the RAG5Ј͞RAG3Ј combination of primers to amplify RAG2 sequences from genomic DNA as an internal standard. PCRs were cycled 30 times in a Hypercell Biological thermal cycler (MJ Research, Cambridge, MA) as described elsewhere (26). VJ L sequences were cloned into pCR II (Invitrogen) and sequenced by the Sheldon Biolabs (McGill University).…”

mentioning

confidence: 99%

Development of B cells expressing surface immunoglobulin molecules that lack V(D)J-encoded determinants in the avian embryo bursa of Fabricius

Sayegh

Demaries

Iacampo

et al. 1999

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

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Immunoglobulin gene rearrangement in avian B cell precursors generates surface Ig receptors of limited diversity. It has been proposed that specificities encoded by these receptors play a critical role in B lineage development by recognizing endogenous ligands within the bursa of Fabricius. To address this issue directly we have introduced a truncated surface IgM, lacking variable region domains, into developing B precursors by retroviral gene transfer in vivo. Cells expressing this truncated receptor lack endogenous surface IgM, and the low level of endogenous Ig rearrangements that have occurred within this population of cells has not been selected for having a productive reading frame. Such cells proliferate rapidly within bursal epithelial buds of normal morphology. In addition, despite reduced levels of endogenous light chain rearrangement, those light chain rearrangements that have occurred have undergone variable region diversification by gene conversion. Therefore, although surface expression of an Ig receptor is required for bursal colonization and the induction of gene conversion, the specificity encoded by the prediversified receptor is irrelevant and, consequently, there is no obligate ligand for V(D)Jencoded determinants of prediversified avian cell surface IgM receptor.The rearrangement of chicken Ig genes generates minimal antibody diversity. At the light chain (L) locus, the unique, functional V L 1 gene rearranges to the unique J L segment in all B cells (1). Similarly, at the heavy chain (H) locus, unique V H 1 and J H genes undergo rearrangement with a family of highly conserved D H elements to form a VDJ H complex of limited diversity (2, 3). Junctional diversity is limited further because of the lack of N nucleotide additions in chicken V(D)J junctions (4). A diverse repertoire of B cell specificities is generated by somatic gene-conversion events in which VD H and V L sequences in functionally rearranged VDJ H and VJ L genes are replaced by homologous sequences from upstream V L and V H pseudogenes (⌿V L and ⌿V H ) (2, 5-7).The bursa of Fabricius is the primary site of B cell lymphopoiesis in avian species, and surgical or chemical ablation of the chicken bursa profoundly disrupts the normal progression of B cell development and the generation of diversity by gene conversion (reviewed in refs. 7-10). The bursa is colonized by a single wave of B cell precursors during embryogenesis starting at about embryonic day 8 (E8) and lasting about a week (11). Within the bursa, B cell precursors first are observed in the mesenchymal tissue, and 20,000-40,000 precursors subsequently migrate across the bursal epithelial basement membrane and begin to proliferate in oligoclonal clusters or epithelial buds from which the discrete follicles of the mature bursa are derived (12, 13).Surface Ig (sIg) ϩ B cell precursors first are observed by about E9-E10, and the frequency of such cells increases rapidly during the embryonic period (14). Although Ig gene rearrangement is not intrinsically biased towar...

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“…The first DH-JH joints in the heavy chain locus can be detected in the yolk sac on embryonic day 5 or 6 (Reynaud et al, 1992). Rearrangement of V(D)J segments is stochastic in the chicken, and frequently VJ recombination in the light chain locus precedes VDJ recombination at the heavy chain locus (Benatar et al, 1992). V(D)J recombination at either locus is virtually complete by embryonic day 15 (Reynaud et al, 1992).…”

Section: Prebursal Stagementioning

confidence: 99%

Immunoglobulin gene conversion: Insights from bursal B cells and the DT40 cell line

Arima¹,

Buerstedde²

2004

Developmental Dynamics

105

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Stochastic rearrangement of immunoglobulin variable-region genes in chicken B-cell development.

Cited by 52 publications

References 33 publications

The Cytoplasmic Domain of Igα Is Necessary and Sufficient to Support Efficient Early B Cell Development

The Cytoplasmic Domain of Igα Is Necessary and Sufficient to Support Efficient Early B Cell Development

Development of B cells expressing surface immunoglobulin molecules that lack V(D)J-encoded determinants in the avian embryo bursa of Fabricius

Immunoglobulin gene conversion: Insights from bursal B cells and the DT40 cell line

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