An Interleukin-2 Signal Relieves BSAP (Pax5)-Mediated Repression of the Immunoglobulin J Chain Gene

Rinkenberger, Julie L.; Wallin, Jeffrey J.; Johnson, Kirk W.; Koshland, Marian Elliott

doi:10.1016/s1074-7613(00)80263-0

Cited by 109 publications

(94 citation statements)

References 44 publications

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“…Although we found a correlation between C͞EBP␣ expression level and Pax5 down-regulation in proB cells, we cannot exclude the possibility that Pax5 silencing in IL-2-stimulated CLPs occurs as a consequence of IL-2R signaling independent of C͞EBP␣ expression level (26). Upon IL-2 stimulation or introduction of C͞EBP␣ in CLPs and proB cells, another B cell-specific transcription factor specification factor, EBF, was also downregulated in addition to Pax5.…”

Section: Discussionmentioning

confidence: 58%

Antagonistic effect of CCAAT enhancer-binding protein-α and Pax5 in myeloid or lymphoid lineage choice in common lymphoid progenitors

Hsu

Fleischman

Lai

et al. 2006

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

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Section: Discussionmentioning

confidence: 58%

Antagonistic effect of CCAAT enhancer-binding protein-α and Pax5 in myeloid or lymphoid lineage choice in common lymphoid progenitors

Hsu

Fleischman

Lai

et al. 2006

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

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“…4), including CD19, LEF, N-myc, mb-1, and PD1, although these are unlikely to be critical for B cell development (5). BSAP is active later in B cell development, potentially through binding sites in murine heavy (6) and light chain 3Ј enhancers (7), J chain, (8), blk (9), CD72 (10), and RAG-2 promoter (11). A number of observations suggest that BSAP function can be modulated by its interaction with other proteins.…”

mentioning

confidence: 99%

BSAP (Pax5)-Importin α1 (Rch1) Interaction Identifies a Nuclear Localization Sequence

Kovac¹,

Emelyanov²,

Singh³

et al. 2000

Journal of Biological Chemistry

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BSAP (Pax5) is a transcription factor expressed exclusively in the developing midbrain, testes, pro-B cells, pre-B cells, and mature B cells (1). When the Pax5 gene was inactivated in mice by targeted homologous recombination, defects in the midbrain and in B cell lymphopoiesis were observed, including complete abrogation of fetal B lymphopoiesis and incomplete VH gene construction in adult bone marrow (2). Recent studies have reported that preBI cells from BSAP -/-mice can differentiate in culture or in some cases, in vivo, to a variety of non-B cell types, including macrophages, granulocytes, osteoclasts, T cells, and natural killer cells (3). This suggests a role for BSAP not only in promoting B cell development but also in eliminating other developmental possibilities.Some target genes for BSAP have been identified (reviewed in Ref. 4), including CD19, LEF, N-myc, mb-1, and PD1, although these are unlikely to be critical for B cell development (5). BSAP is active later in B cell development, potentially through binding sites in murine heavy (6) and light chain 3Ј enhancers (7), J chain, (8), blk (9), CD72 (10), and RAG-2 promoter (11). A number of observations suggest that BSAP function can be modulated by its interaction with other proteins. For example, it has been shown that BSAP down-regulates the murine 3Ј IgH enhancer hs1,2 in B cell lines in concert with other transcription factors that also bind to this enhancer (12). These factors include octamer-binding proteins, B-binding proteins, and a G-rich DNA-binding protein. Using a GST 1 pulldown assay, we detected interaction of BSAP with the POU domains of Oct-1 and Oct-2 (12). Other investigators have shown that the DNA-binding domain of BSAP interacts with and recruits Ets family proteins to ternary complexes with the mb-1 promoter in pre-B cells (13). BSAP has also been shown to interact with the acute myeloid leukemia protein, AML, in the regulation of the blk promoter (9) and with PU.1 (14). We have therefore proposed to identify proteins that interact with BSAP using a yeast two-hybrid assay.BSAP is a member of the highly conserved Using the central domain of BSAP as a bait in the two-hybrid assay system, we report here a strong interaction with Rch1

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“…The selected plasmid was sequenced to verify the base substitutions. Mutations introduced into the JC motif have been described previously (7).…”

Section: Methodsmentioning

confidence: 99%

“…In the case of the J chain promoter, BSAP acts as a repressor: base changes in the BSAP-binding site result in a relief of repression in J chain negative cell lines (7). An IL-2 or IL-5 signal delivered to mature B cells has been shown to cause a progressive decrease in BSAP transcripts that extends from the presecretor immunoblast through the plasma cell stages (7).…”

mentioning

confidence: 99%

B Cell-specific Activator Protein Prevents Two Activator Factors from Binding to the Immunoglobulin J ChainPromoter until the Antigen-driven Stages of B Cell Development

Wallin¹,

Rinkenberger²,

Rao³

et al. 1999

Journal of Biological Chemistry

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The immunoglobulin J chain gene is inducibly transcribed in mature B cells upon antigen recognition and a signal from interleukin-2 (IL-2). B cell-specific activator protein (BSAP), a transcription factor that silences J chain transcription, has been identified as a nuclear target of the IL-2 signal. The levels of BSAP progressively decrease in response to IL-2 and this change correlates with the differentiation of B cells into antibody secreting plasma cells. Here we report the binding of the upstream stimulatory factor (USF) to an E-box motif immediately upstream from the BSAP site on the J chain promoter. Mutations in the USF binding motif significantly decrease J chain promoter activity in J chain expressing B cell lines. We also show that a functional relationship exists between USF and a second J chain positive-regulating factor, B-MEF2, using co-immunoprecipitation assays and transfections. Finally, we provide evidence that the binding of BSAP prevents USF and B-MEF2 from interacting with the J chain promoter during the antigen-independent stages of B cell development. It is not until the levels of BSAP decrease during the antigen-driven stages of B cell development that both USF and B-MEF2 are able to bind to their respective promoter elements and activate J chain transcription.During a primary immune response to foreign antigens, mature B cells become activated and differentiate into pentamer IgM-secreting plasma cells. One of the critical events in this process is the synthesis of the immunoglobulin J chain protein required for the assembly and secretion of pentamer IgM antibody (1). Studies of both normal B cells and model B cell lines have shown that J chain synthesis is tightly regulated at the transcriptional level. For efficient J chain transcription to occur, activation signals from both the B cell receptor and the interleukin-2 (IL-2) 1 or IL-5 receptors are needed. Correlating with IL-2/IL-5 induced gene transcription is the appearance of a DNase I-hypersensitive site (bp Ϫ170 to ϩ88) on the J chain promoter of activated B cells (2, 3). The full activity of the J chain promoter is contained within this hypersensitive region, as has been shown using 5Ј deletion mutants in a CAT reporter system (4).Three regulatory elements have been found to be present within this region. These include a T-rich positive regulatory element denoted JA (Ϫ74 to Ϫ60), a purine-rich sequence (Ϫ58 to Ϫ47) denoted JB, and a repressive motif, JC (Ϫ127 to Ϫ110) (5-7). The factor interacting with the JA sequence has recently been identified to be a member of the myocyte enhancer factor-2 (MEF-2) family that is expressed in the B cell lineage, denoted B-MEF2 (5). The JB element has previously been shown to interact with transcription factor PU.1, a member of the Ets family of transcription factors expressed in hematopoietic lineages including monocytes, macrophages, and B lymphoid cells (6). Mutational analyses in J chain positive cell lines have indicated positive regulatory roles for both PU.1 and B-MEF2; base changes tha...

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An Interleukin-2 Signal Relieves BSAP (Pax5)-Mediated Repression of the Immunoglobulin J Chain Gene

Cited by 109 publications

References 44 publications

Antagonistic effect of CCAAT enhancer-binding protein-α and Pax5 in myeloid or lymphoid lineage choice in common lymphoid progenitors

Antagonistic effect of CCAAT enhancer-binding protein-α and Pax5 in myeloid or lymphoid lineage choice in common lymphoid progenitors

BSAP (Pax5)-Importin α1 (Rch1) Interaction Identifies a Nuclear Localization Sequence

B Cell-specific Activator Protein Prevents Two Activator Factors from Binding to the Immunoglobulin J ChainPromoter until the Antigen-driven Stages of B Cell Development

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