The surrogate light chain in B-cell development

Melchers, Fritz; Karasuyama, Hajime; Haasner, Dirk; Bauer, Steven R.; Kudo, Akira; Sakaguchi, Nobuo; Jameson, Bradford A.; Rolink, Antonius

doi:10.1016/0167-5699(93)90060-x

Cited by 244 publications

(136 citation statements)

References 56 publications

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“…One possible explanation is that the Ig domain of VpreB may be able to successfully compete with the unique region of 5͞14.1 for binding to the J homology region. In the absence of VpreB, the unique region might interact with the J homology region as first proposed by Melchers et al (1) and in some way inhibit the folding of the remaining portion of 5͞14.1; however, deletion of the extra ␤ strand did not relieve this inhibition. Alternatively, the 5͞14.1 unique region could directly associate with any of the remaining ␤ strands in 5͞14.1 and alter their folding and prevent oxidation.…”

Section: Discussionmentioning

confidence: 94%

Novel mechanisms control the folding and assembly of λ5/14.1 and VpreB to produce an intact surrogate light chain

Minegishi

Hendershot

Conley

1999

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

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Surrogate light chain, which escorts the mu heavy chain to the cell surface, is a critical component of the pre-B cell receptor complex. The two proteins that comprise the surrogate light chain, VpreB and 5͞14.1, contain both unique regions and Ig-like domains. The unique regions have been postulated to function in the assembly of the surrogate light chain. However, by using transient transfection of COS7 cells, we show that deletion of the unique regions of both proteins did not inhibit the assembly of surrogate light chain. Instead, in vivo folding studies showed that the unique region of 5͞14.1 acts as an intramolecular chaperone by preventing the folding of this protein when it is expressed in the absence of its partner, VpreB. The Ig domains of both 5͞14.1 and VpreB are atypical. The one in VpreB lacks one of the canonical ␤ strands whereas the one in 5͞14.1 has an extra ␤ strand. Deletion of the extra ␤ strand in 5͞14.1 completely abrogated the formation of the surrogate light chain, demonstrating that complementation of the incomplete Ig domain in VpreB by the extra ␤ strand in 5͞14.1 was necessary and sufficient for the folding and assembly of these proteins. Our studies reveal two novel mechanisms for regulating surrogate light chain formation: (i) the presence of an intramolecular chaperone that prevents folding of the unassembled subunit but that remains part of the mature assembled protein, and (ii) splitting an Ig domain between two proteins to control their folding and assembly.

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Section: Discussionmentioning

confidence: 94%

Novel mechanisms control the folding and assembly of λ5/14.1 and VpreB to produce an intact surrogate light chain

Minegishi

Hendershot

Conley

1999

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

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“…The locus contains the l5 and VpreB1 genes, which are expressed in pro-and pre-B cells (Melchers et al, 1993). The genes encode the components of the surrogate light chain, which forms part of the pre-B-cell receptor.…”

Section: Results and Discussion H33 Is Enriched At Promoters Of Exprmentioning

confidence: 99%

Variant histone H3.3 marks promoters of transcriptionally active genes during mammalian cell division

Chow¹,

Georgiou²,

Szutorisz³

et al. 2005

EMBO Reports

153

124

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Variant histone H3.3 is incorporated into nucleosomes by a mechanism that does not require DNA replication and has also been implicated as a potential mediator of epigenetic memory of active transcriptional states. In this study, we have used chromatin immunoprecipitation analysis to show that H3.3 is found mainly at the promoters of transcriptionally active genes. We also show that H3.3 combines with H3 acetylation and K4 methylation to form a stable mark that persists during mitosis. Our results suggest that H3.3 is deposited principally through the action of chromatin-remodelling complexes associated with transcriptional initiation, with deposition mediated by RNA polymerase II elongation having only a minor role.

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“…The physiological role of the pre-BR complex during early B cell differentiation is not fully elucidated [35]. However, analysis of h5 gene-disrupted mice suggests that pre-BR may promote a survival signal to the pre-B cells [36].…”

Section: Discussionmentioning

confidence: 99%

IL-7 sensitizes human pre-B cells but not pro-B cells to Fas/APO-1 (CD95)-mediated apoptosis

Lévy¹,

Benlagha²,

Buzyn³

et al. 1997

Clinical and Experimental Immunology

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SUMMARYHomeostasis of human B cell development is maintained by a complex network of cytoplasmic and surface expressed molecules. Abnormalities in this process may result in the expansion of malignant B cell precursors in B lineage acute lymphoblastic leukaemia (ALL). ALL cells share surface antigens with normal early precursor B cells. We have studied here the role of Fas/APO-1 (CD95) antigen on leukaemic precursor B cell line growth and survival, and the modulation of its effects by signals involved in normal early B cell development. Four ALL cell lines representative of the early steps of B cell differentiation are shown to express surface Fas/APO-1 (CD95) antigen and to undergo apoptosis in the presence of anti-Fas cross-linking antibodies. This effect is strongly enhanced when pre-B, but not pro-B cells, are pretreated with IL-7 but not with IL-2, IL-3, IL-4 or IL-10. Furthermore, pre-B cell death induced by anti-Fas antibodies in combination with IL-7 is increased upon pre-B receptor but not CD19 cross-linking. Bcl-2 and Bax protein expression is not influenced by IL-7 or pre-BR stimulation in either pro-B or pre-B cell lines. These results indicate that signals involved in normal early B cell development can modulate the Fas (CD95)-mediated apoptosis of leukaemic precursor B cells.

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The surrogate light chain in B-cell development

Cited by 244 publications

References 56 publications

Novel mechanisms control the folding and assembly of λ5/14.1 and VpreB to produce an intact surrogate light chain

Novel mechanisms control the folding and assembly of λ5/14.1 and VpreB to produce an intact surrogate light chain

Variant histone H3.3 marks promoters of transcriptionally active genes during mammalian cell division

IL-7 sensitizes human pre-B cells but not pro-B cells to Fas/APO-1 (CD95)-mediated apoptosis

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