Interleukin-5 (IL-5) and IL-6 define two molecularly distinct pathways of B-cell differentiation.

Randall, Troy D.; Lund, Frances E.; Brewer, J W; Aldridge, C; Wall, R; Corley, Ronald B.

doi:10.1128/mcb.13.7.3929

Cited by 21 publications

(19 citation statements)

References 25 publications

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“…Indeed, IL-6 and TGF-b have been shown to induce neuronal differentiation and to inhibit myogenesis [20]. The proinflammatory cytokines increased secretion of both IL-6, which may help differentiation of B cells and activation of T cells in the inflammatory milieu [21], and TGF-b,…”

Section: Infiltration Of Skeletal Muscle By Inflammatory Cells Has Beenmentioning

confidence: 99%

A variety of cytokines and immunologically relevant surface molecules are expressed by normal human skeletal muscle cells under proinflammatory stimuli

Nagaraju

Raben

Merritt

et al. 1998

Clinical and Experimental Immunology

155

120

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SUMMARYMuscle is an attractive target for gene therapy and for immunization with DNA vaccines and is also the target of immunological injury in myositis. It is important therefore to understand the immunologic capabilities of muscle cells themselves. In this study, we show that proinflammatory stimuli induce the expression of other cytokines such as IL-6, transforming growth factor-beta (TGF-b), and granulocytemacrophage colony-stimulating factor (GM-CSF) by muscle cells themselves, as well as the upregulation of human leucocyte antigen (HLA) class I, class II and intercellular adhesion molecule-1 (ICAM-1). Thus, muscle cells have an inherent ability to express and respond to a variety of cytokines and chemokines. The levels of HLA class I, class II and ICAM-1 in inflamed muscle may be affected by the secreted products of the stimulation.

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Section: Infiltration Of Skeletal Muscle By Inflammatory Cells Has Beenmentioning

confidence: 99%

A variety of cytokines and immunologically relevant surface molecules are expressed by normal human skeletal muscle cells under proinflammatory stimuli

Nagaraju

Raben

Merritt

et al. 1998

Clinical and Experimental Immunology

155

120

View full text Add to dashboard Cite

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“…1A and Ref. 28), use of these stimuli allows one to potentially distinguish events related to proliferation rather than differentiation. Immunoblot analysis using a rabbit antibody that recognizes both the p30 and p54 forms of XBP-1 was performed on CH12 cells harvested at 24-and 48-h intervals of culture under various conditions.…”

Section: Expression Of P54xbp-1 In Differentiating B Cells-expres-mentioning

confidence: 99%

Activation of an Unfolded Protein Response during Differentiation of Antibody-secreting B Cells

Gass

Gifford

Brewer

2002

Journal of Biological Chemistry

277

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The unfolded protein response pathway (UPR) is believed to detect and compensate for excessive protein accumulation in the endoplasmic reticulum (ER). The UPR can be induced by pharmacological agents that perturb ER functions, but may also occur during cellular developmental processes such as the transition of B-lymphocytes into antibody-secreting plasma cells. Here we show that major UPR components are activated in B cells stimulated to secrete antibody. Increased expression of UPR targets including the ER chaperones BiP and GRP94 and the transcription factor XBP-1 initiates early in the differentiation program prior to upregulated synthesis of Ig chains. Furthermore, these same kinetics are observed during differentiation for cleavage of the ER-localized ATF6␣ protein and splicing of XBP-1 mRNA to generate p50ATF6␣ and p54XBP-1, the two known UPR transcriptional activators. All of these UPR events reach maximal levels once Ig synthesis and secretion are markedly induced. Interestingly, these events are not accompanied by expression of CHOP, a transcription factor induced by ER stress agents commonly used to investigate the UPR. These results suggest that a physiological UPR elicited during differentiation of B-lymphocytes into high-rate secretory cells may be distinct from the UPR defined by agents that disrupt protein maturation in the ER.

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“…These included c-Rel (55), NF-B1 (56), and Ig L chain (10) Abs. B, Signals from autoradiographs shown in A were quantitated by densitometry.…”

Section: Selective Reductions In Ib⑀ Mrna and Changes In Gene Expressmentioning

confidence: 99%

Reductions in IκBε and Changes in NF-κB Activity during B Lymphocyte Differentiation

Doerre

Mesires

Daley

et al. 2005

The Journal of Immunology

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The levels and stability of IκBε have been examined in unstimulated and stimulated splenic B cells and compared with that of IκBα and IκBβ. Primary murine splenic B cells but not T cells were found to contain high levels of IκBε protein, equivalent to levels of the abundant IκBα. Most agents that activate IκBα and IκBβ degradation do not induce rapid degradation of IκBε. Interestingly, however, the levels of IκBε, but not of IκBα or IκBβ, are dramatically reduced upon the stimulation of B cells both in vivo and in vitro. Since IκBε exhibits substrate specificity for NF-κB Rel homodimers, this suggested the possibility that changes in NF-κB-responsive genes might also occur during this transition. Consistent with this hypothesis, we found that a NF-κB reporter construct sensitive to p65/RelA homodimers is activated at the time that IκBε levels decline following B cell stimulation. In IgG+ B cell lines, which contain low levels of IκBε, this same reporter construct was inactive, suggesting that the increases in Rel homodimer activity that accompany B cell stimulation are transient. However, there are differences in the level of expression of NF-κB-responsive genes in these IgG+ B cell lines compared with their IgM+ counterparts. From these data, we conclude that there are transient changes in NF-κB activity due to reductions in IκBε, which might contribute to long-term, persistent changes that accompany B cell differentiation. We propose an important role for IκBε in the differential regulation of nuclear NF-κB activity in stimulated B cells.

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Interleukin-5 (IL-5) and IL-6 define two molecularly distinct pathways of B-cell differentiation.

Cited by 21 publications

References 25 publications

A variety of cytokines and immunologically relevant surface molecules are expressed by normal human skeletal muscle cells under proinflammatory stimuli

A variety of cytokines and immunologically relevant surface molecules are expressed by normal human skeletal muscle cells under proinflammatory stimuli

Activation of an Unfolded Protein Response during Differentiation of Antibody-secreting B Cells

Reductions in IκBε and Changes in NF-κB Activity during B Lymphocyte Differentiation

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