Influence of immunoglobulin heavy- and light-chain expression on B-cell differentiation.

Young, Faith; Ardman, Blair; Shinkai, Yoichi; Lansford, Rusty; Blackwell, T. Keith; Mendelsohn, Monica; Rolink, A G; Melchers, Fritz; Alt, Frederick W.

doi:10.1101/gad.8.9.1043

Cited by 187 publications

(162 citation statements)

References 91 publications

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“…Second, expression of a rearranged p heavy-chain transgene in Pax5 mutant mice did not allow B lymphocytes to advance in B-cell development (C. Thevenin and M. Busslinger, unpubl. ) in contrast with the situation observed with RAG-deficient mice where complementation with a p transgene facilitates progression to the small pre-B cell stage Spanopoulou et al 1994;Young et al 1994). The lack of complementation therefore indicates that the failure to undergo Vy^-to-Dj^lyi rearrangements is unlikely to be the reason for the developmental block observed in the bone marrow of Pax5 mutant mice.…”

Section: Paxs and The B-cell-specific Control Of V(d)j Recombinationcontrasting

confidence: 44%

Essential functions of Pax5 (BSAP) in pro-B cell development: difference between fetal and adult B lymphopoiesis and reduced V-to-DJ recombination at the IgH locus.

Nutt¹,

Urbánek²,

Rolink³

et al. 1997

Genes Dev.

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375

372

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Section: Paxs and The B-cell-specific Control Of V(d)j Recombinationcontrasting

confidence: 44%

Essential functions of Pax5 (BSAP) in pro-B cell development: difference between fetal and adult B lymphopoiesis and reduced V-to-DJ recombination at the IgH locus.

Nutt¹,

Urbánek²,

Rolink³

et al. 1997

Genes Dev.

Self Cite

375

372

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“…Tonic signaling, which derives from an intact BCR (42) and is sufficient for differentiation to a splenic B cell (18), appears to be intact in 6-1/V 1A B cells. We have previously shown that the 6-1 H chain and V 1A L chain can pair and be secreted by cells of a transfected cell line (27), and bone marrow immature and splenic transitional B cells in 6-1/V 1A/RAG-1 Ϫ/Ϫ mice are IgM high (Fig.…”

Section: Discussionmentioning

confidence: 99%

Evidence for a Ligand-Mediated Positive Selection Signal in Differentiation to a Mature B Cell

Wang

Clarke

2003

The Journal of Immunology

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Positive selection is required for B cell differentiation, as indicated by the requirement for expression of the pre-B cell receptor (pre-BCR) and the BCR at the pre-B and immature B cell stages, respectively. Positive selection mediated by a tonic signal from these receptors is sufficient to drive B cell differentiation beyond the pre-B and immature B cell stages, but it is unclear whether additional positive selection signals are required for differentiation to a mature B-2 cell. We have identified a population of Ig transgenic B cells that differentiatively arrest at a transitional B cell stage in the spleen. They exhibit no evidence of Ag encounter or negative selection and can differentiate to mature B-2 cells in vivo upon weak BCR stimulation or adoptive transfer to irradiated hosts. These data are consistent with a requirement for a ligand-mediated BCR signal for differentiation to a mature B-2 cell.

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“…Sykdeficient mice (Syk tm1Tyb/tm1Tyb , Syk -/-) on a C57BL/6J background were generated in our laboratory [12]. Other mouse strains used in this study: mice deficient in Rag1 on a C57BL/ 10ScSn background (Rag1 -/-) [40], mice deficient in Zap70 on B10.D2 and C57BL/6J backgrounds (Zap70 -/-) [17], and mice with a targeted disruption in the membrane-tethering exon of the immunoglobulin l heavy chain (lMT) [30], mice deficient in TCR a chain (TCRa -/-) [41], and HC186 transgenic mice expressing a rearranged immunoglobulin l heavy chain [42], all on a C57BL/6J background. B10.D2, C57BL/10ScSn, C57BL/6J, and B6.SJL inbred mouse strains were bred in-house at NIMR.…”

Section: Micementioning

confidence: 99%

Redundant role for Zap70 in B cell development and activation

Fallah-Arani

Schweighoffer²,

Vanes³

et al. 2008

Eur J Immunol

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Expression of the Syk family tyrosine kinase Zap70 is strongly correlated with poor clinical outcome in chronic lymphocytic leukemia, the most common human leukemia characterized by B cell accumulation. The expression of Zap70 may reflect the specific cell of origin of the tumor or may contribute to pathology. Thus, the normal role of Zap70 in B cell physiology is of great interest. While initial studies reported that Zap70 expression in the mouse was limited to T and NK cells, more recent work has shown expression in early B cell progenitors and in splenic B cells, suggesting that the kinase may play a role in the development or activation of B cells. In this study, we show that Zap70 is expressed in all developing subsets of B cells as well as in recirculating B cells, marginal zone B cells and peritoneal B1 cells. Analysis of Zap70-deficient mice shows no unique role for Zap70 in either the development of B cells or in their in vitro and in vivo activation. However, we show that Zap70 can rescue the defective positive selection of immature B cells into the recirculating pool in Syk-deficient mice, demonstrating functional redundancy between these two kinases.

show abstract

Influence of immunoglobulin heavy- and light-chain expression on B-cell differentiation.

Abstract: To study the influence of immunoglobulin heavy-chain (HC) and light-chain (LC) expression in promoting

Cited by 187 publications

References 91 publications

Essential functions of Pax5 (BSAP) in pro-B cell development: difference between fetal and adult B lymphopoiesis and reduced V-to-DJ recombination at the IgH locus.

Essential functions of Pax5 (BSAP) in pro-B cell development: difference between fetal and adult B lymphopoiesis and reduced V-to-DJ recombination at the IgH locus.

Evidence for a Ligand-Mediated Positive Selection Signal in Differentiation to a Mature B Cell

Redundant role for Zap70 in B cell development and activation

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