Posttranscriptional regulation of Bruton's tyrosine kinase expression in antigen receptor-stimulated splenic B cells

Nisitani, Sazuku; Satterthwaite, Anne B.; Akashi, Koichi; Weissman, Irving L.; Witte, Owen N.; Wahl, Matthew I.

doi:10.1073/pnas.050583597

Cited by 43 publications

(34 citation statements)

References 58 publications

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“…Moreover, the total concentration of Btk does not change under the same conditions, and remains unchanged in cells pretreated with LPS and stimulated with the complexes. This finding is in contrast to those in studies showing an increase in the Btk expression of B cells (53,54).…”

Section: Discussioncontrasting

confidence: 56%

Bruton’s Tyrosine Kinase Mediates FcγRIIa/Toll-Like Receptor–4 Receptor Crosstalk in Human Neutrophils

Krupa

Fudala

Florence³

et al. 2013

Am J Respir Cell Mol Biol

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Previous observations by our laboratory indicate that the presence of anti-IL-8 autoantibody:IL-8 immune complexes in lung fluids from patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) comprises an important prognostic indicator in the development and ultimate outcome of ALI/ARDS. We also showed that these complexes display proinflammatory activity toward neutrophils through the engagement of FcgRIIa receptors. Because sepsis is one of the most common risk factors for ALI/ARDS, the initial goal of our present study involved investigating the effects of LPS on the expression of FcgRIIa receptors in neutrophils. Our results indicate that LPS triggers an increase in the expression of FcgRIIa on the neutrophil surface, which leads to shortening of the molecular distance between FcgRIIa and Toll-like receptor-4 (TLR4). When such neutrophils are stimulated with anti-IL-8:IL-8 complexes, the TLR4 cascade becomes activated via the engagement of FcgRIIa. The underlying molecular mechanism has been subsequently examined and involves Bruton's tyrosine kinase (Btk). In conclusion, our study reveals the existence of Btk-dependent molecular cooperation between FcgRIIa and TLR4 signaling cascades in LPS-"primed" human neutrophils. Furthermore, we used fluorescence lifetime imaging to study the interactions between TLR4 and FcgRIIa in human alveolar neutrophils from patients with ALI/ARDS. The results from these experiments confirm the existence of the molecular cooperation between TLR4 and FcgRIIa.Keywords: neutrophil; FcуRIIa; TLR4; Btk Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is characterized by diffuse, acute lung injury with a significant increase in both the total number of neutrophils and the proportion of neutrophils within alveolar spaces (1). Although neutrophils constitute only 0.8-3% of nonstructural alveolar cells in normal subjects, they account for 70-80% of the cells in bronchoalveolar (BAL) fluid from patients with ARDS (2, 3). Previous observations by our laboratory indicate that the presence of anti-IL-8 autoantibody:IL-8 immune complexes (IL-8 associated with anti-IL-8 autoantibodies) in lung fluid from patients with ALI/ARDS comprises an important prognostic indicator of the development and ultimate outcome of ALI/ARDS (4-6). In addition, our studies were the first to show that purified anti-IL-8 autoantibody:IL-8 immune complexes display proinflammatory activity toward neutrophils and endothelial cells through the engagement of FcgRIIa (7-9). Further, when we examined lung tissue from patients with lung injury for anti-IL-8 autoantibody: IL-8 immune complexes, we found these complexes in the lungs of patients with ARDS, in association with FcgRIIa (10). Our previous findings also indicate that the expression of FcgRIIa is substantially increased in the lungs of patients with ARDS (9, 10).Sepsis is a major risk factor for the development of ALI/ARDS, and LPS is a likely cause of progression to ALI/ARDS (1). Tolllike receptor-4 (TLR4), a receptor for LPS, ...

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Section: Discussioncontrasting

confidence: 56%

Bruton’s Tyrosine Kinase Mediates FcγRIIa/Toll-Like Receptor–4 Receptor Crosstalk in Human Neutrophils

Krupa

Fudala

Florence³

et al. 2013

Am J Respir Cell Mol Biol

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“…In chicken DT40 B cells, Btk bound Fas directly, interfering with signaling for cell death, such that Btk-deficient DT40 cells were much more sensitive to Fas killing than wild-type (WT) control cells. Combined with the observation that Btk protein expression was up-regulated following sIg engagement (43), these results raise the possibility that Btk may be responsible for sIg-induced Fas resistance, either as a signaling intermediary, or as a terminal inhibitor of the Fas death pathway. The present study was conducted to examine the role of Btk in promoting sIg-induced Fas resistance, and the capacity of Btk to modulate the sensitivity of B cells to Fas killing.…”

mentioning

confidence: 74%

BCR Engagement Induces Fas Resistance in Primary B Cells in the Absence of Functional Bruton’s Tyrosine Kinase

Tumang

Negm

Solt

et al. 2002

The Journal of Immunology

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B cell susceptibility to Fas-mediated apoptosis is regulated in a receptor-specific fashion. CD40 engagement produces marked sensitivity to Fas killing, whereas surface Ig (sIg) engagement blocks Fas signaling for cell death in otherwise sensitive, CD40-stimulated B cell targets, and thus, induces a state of Fas resistance. The signaling mediator, Bruton’s tyrosine kinase (Btk), is required for certain sIg-triggered responses, and Btk is reported to directly bind Fas and block Fas-mediated apoptosis. For these reasons, the role of Btk as a mediator of sIg-induced Fas resistance was examined. Dysfunction of Btk through mutation, and absence of Btk through deletion did not interfere with induction of Fas resistance by anti-Ig. This may be due, at least in part, to induction of Btk-dependent Bcl-2 family members by anti-Ig after CD40 ligand treatment. However, the susceptibility to Fas-mediated apoptosis of B cell targets stimulated by CD40 ligand alone was increased in the absence of Btk. These results indicate that Fas resistance produced by sIg triggering does not require Btk, but suggests that in certain situations Btk modulates B cell susceptibility to Fas killing.

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“…Intracellular levels of Btk may play an important role in a quantitative increase in BCR signaling with B cell maturation. Nisitani et al showed that Btk protein levels in splenic B cells are maximally increased (7-to 10-fold) within 4 h of BCR stimulation by a posttranscriptional mechanism involving Btk and PI3K (39). This up-regulation also occurs in vivo after T cell-dependent or T cell-independent immunization.…”

Section: Btk and Nf-b Positive Autoregulatory Loop Downstream Of Bcrmentioning

confidence: 96%

B Cell Receptor and BAFF Receptor Signaling Regulation of B Cell Homeostasis

Khan

2009

The Journal of Immunology

150

112

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B lymphocyte homeostasis depends on tonic and induced BCR signaling and receptors sensitive to trophic factors, such as B cell-activating factor receptor (BAFF-R or BR3) during development and maintenance. This review will discuss growing evidence suggesting that the signaling mechanisms that maintain B cell survival and metabolic fitness during selection at transitional stages and survival after maturation rely on cross-talk between BCR and BR3 signaling. Recent findings have also begun to unravel the molecular mechanisms underlying this crosstalk. In this review I also propose a model for regulating the amplitude of BCR signaling by a signal amplification loop downstream of the BCR involving Btk and NF-κB that may facilitate BCR-dependent B cell survival as well as its functional coupling to BR3 for the growth and survival of B lymphocytes.

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Posttranscriptional regulation of Bruton's tyrosine kinase expression in antigen receptor-stimulated splenic B cells

Cited by 43 publications

References 58 publications

Bruton’s Tyrosine Kinase Mediates FcγRIIa/Toll-Like Receptor–4 Receptor Crosstalk in Human Neutrophils

Bruton’s Tyrosine Kinase Mediates FcγRIIa/Toll-Like Receptor–4 Receptor Crosstalk in Human Neutrophils

BCR Engagement Induces Fas Resistance in Primary B Cells in the Absence of Functional Bruton’s Tyrosine Kinase

B Cell Receptor and BAFF Receptor Signaling Regulation of B Cell Homeostasis

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