Cutting Edge: B Cell Antigen Receptor Signaling Occurs Outside Lipid Rafts in Immature B Cells

Sproul, Tim W.; Malapati, Sunil; Kim, Julie; Pierce, Susan K.

doi:10.4049/jimmunol.165.11.6020

Cited by 107 publications

(85 citation statements)

References 18 publications

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“…Translocation of the BCR into lipid rafts has also been shown to result in the recruitment of several components of the BCR signal cascade, including BLNK, phosphatidylinositol 3 kinase, VAV, and Btk (17,18,32). Evidence that the rafts play important physiological roles in B cell activation has been provided by the recent observations that BCR access to rafts is controlled during B cell development (19), by viral infection (20), and by the essential B cell coreceptor CD19 (Cherukuri, Sohn, and Pierce, unpublished observations). Thus, rafts appear to play key roles in the initiation and regulation of BCR signaling.…”

Section: Discussionmentioning

confidence: 97%

“…Thus, cross-linking or oligomerizing the BCR results in a change in the BCR such that it preferentially localizes to the cholesterol-and sphingolipid-rich microdomains of the plasma membrane. Recent evidence indicates that BCR entry into lipid rafts is regulated during B cell development (19) and by viral infection by EBV (20), suggesting that rafts play important physiological roles as platforms for B cell signaling.…”

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confidence: 99%

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Translocation of the B Cell Antigen Receptor into Lipid Rafts Reveals a Novel Step in Signaling

Cheng

Brown

Song

et al. 2001

The Journal of Immunology

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132

104

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The cross-linking of the B cell Ag receptor (BCR) leads to the initiation of a signal transduction cascade in which the earliest events involve the phosphorylation of the immunoreceptor tyrosine-based activation motifs of Igα and Igβ by the Src family kinase Lyn and association of the BCR with the actin cytoskeleton. However, the mechanism by which BCR cross-linking initiates the cascade remains obscure. In this study, using various A20-transfected cell lines, biochemical and genetic evidence is provided that BCR cross-linking leads to the translocation of the BCR into cholesterol- and sphingolipid-rich lipid rafts in a process that is independent of the initiation of BCR signaling and does not require the actin cytoskeleton. Translocation of the BCR into lipid rafts did not require the Igα/Igβ signaling complex, was not dependent on engagement of the FcR, and was not blocked by the Src family kinase inhibitor PP2 or the actin-depolymerizing agents cytochalasin D or latrunculin. Thus, cross-linking or oligomerization of the BCR induces the BCR translocation into lipid rafts, defining an event in B cell activation that precedes receptor phosphorylation and association with the actin cytoskeleton.

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Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

Translocation of the B Cell Antigen Receptor into Lipid Rafts Reveals a Novel Step in Signaling

Cheng

Brown

Song

et al. 2001

The Journal of Immunology

Self Cite

132

104

View full text Add to dashboard Cite

show abstract

“…While there was significant BCR immunoreactivity found in lipid raft fractions in resting cells, a slightly gradual increase in the intensity of BCR bands in fractions 5-9 of the lysates derived from stimulated cells was evident, although the extent of the translocation appeared to be less significant than that for HS1. A previous report had described that translocation of BCR into rafts is more efficient in mature B lymphocyte CH27 cells than in WEHI-231 cells (28). Therefore, we analyzed the association of BCR and HS1 with raft fractions in the lysates from CH27 cells as well.…”

Section: Hs1 Is Cotranslocated Into Lipid Rafts With Arp2/3 Complex Amentioning

confidence: 99%

Syk-mediated Tyrosine Phosphorylation Is Required for the Association of Hematopoietic Lineage Cell-specific Protein 1 with Lipid Rafts and B Cell Antigen Receptor Signalosome Complex

Hao¹,

Carey

Zhan³

2004

Journal of Biological Chemistry

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Reintroducing a Syk construct into the Syk knock-out cells recovered effectively both tyrosine phosphorylation and translocation of HS1 into lipid rafts. In contrast, translocation of HS1 into rafts was normal in a Lyn knock-out B cell line, and an HS1 mutant at the tyrosine residue Tyr 222 targeted by Lyn maintained the ability to partition into rafts upon BCR cross-linking. These data indicate that Syk plays an important role in the translocation of HS1 into lipid rafts and may be responsible for actin assembly recruitment to rafts and subsequent antigen presentations.

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“…However, additional factors including developmental differences in partitioning of BCRassociated signaling components (12,13), basal expression levels of BCL-2 family proteins (14,15), expression/function of * The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C.…”

mentioning

confidence: 99%

The Adaptor Protein HSH2 Attenuates Apoptosis in Response to Ligation of the B Cell Antigen Receptor Complex on the B Lymphoma Cell Line, WEHI-231

Herrin

Groeger

Justement

2005

Journal of Biological Chemistry

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Signals transduced by the B cell antigen receptor (BCR) play a central role in regulating the functional response of the cell to antigen. Depending on the nature of the antigenic signal and the developmental or differentiation state of the B cell, antigen receptor signaling can promote either apoptosis or survival and activation. Understanding the molecular mechanisms underlying BCR-mediated apoptosis constitutes an important area of research because aberrations in programmed cell death can result in the development of autoimmunity or cancer. Expression of the adaptor protein hematopoietic Src homology 2 (HSH2) was found to significantly decrease BCR-mediated apoptosis in the murine WEHI-231 cell line. Analysis of signal transduction pathways activated in response to BCR ligation revealed that HSH2 does not significantly alter total protein tyrosine phosphorylation or Ca 2؉ mobilization. HSH2 does not potentiate the activation-dependent phosphorylation of AKT either. With respect to MAPK activation, HSH2 was not observed to alter the activation of ERK or p38 in response to BCR ligation, but it does significantly potentiate JNK activation. Analysis of processes directly associated with apoptosis revealed that HSH2 inhibits mitochondrial depolarization to a significant degree, whereas it has only a slight effect on caspase activation and poly ADP-ribose polymerase cleavage. BCR-induced apoptosis of WEHI-231 cells is associated with the loss of endogenous HSH2 expression within 12 h, whereas inhibition of apoptosis in response to CD40-mediated signaling leads to stabilization of HSH2 expression. Thus, endogenous HSH2 expression correlates directly with survival of WEHI-231 cells, which supports the hypothesis that HSH2 modulates the apoptotic response through its ability to directly or indirectly promote mitochondrial stability.

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Cutting Edge: B Cell Antigen Receptor Signaling Occurs Outside Lipid Rafts in Immature B Cells

Cited by 107 publications

References 18 publications

Translocation of the B Cell Antigen Receptor into Lipid Rafts Reveals a Novel Step in Signaling

Translocation of the B Cell Antigen Receptor into Lipid Rafts Reveals a Novel Step in Signaling

Syk-mediated Tyrosine Phosphorylation Is Required for the Association of Hematopoietic Lineage Cell-specific Protein 1 with Lipid Rafts and B Cell Antigen Receptor Signalosome Complex

The Adaptor Protein HSH2 Attenuates Apoptosis in Response to Ligation of the B Cell Antigen Receptor Complex on the B Lymphoma Cell Line, WEHI-231

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