B‐Lymphocyte Signal Transduction in Response to Anti‐Immunoglobulin and Bacterial Lipopolysaccharide

DeFranco, A L; Gold, Michael R.; Jakway, James

doi:10.1111/j.1600-065x.1987.tb00504.x

Cited by 91 publications

(44 citation statements)

References 62 publications

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“…sIgM have been extensively investigated (34,35,39,41,42). Our above results suggest that the early events of signal transduction mediated by CD40 differ from those mediated through sIg.…”

Section: Slgm-sediated Tyrosine Phosphorylatioa Differs From That Thrmentioning

confidence: 99%

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CD40 signaling pathway: anti-CD40 monoclonal antibody induces rapid dephosphorylation and phosphorylation of tyrosine-phosphorylated proteins including protein tyrosine kinase Lyn, Fyn, and Syk and the appearance of a 28-kD tyrosine phosphorylated protein.

Faris

Gaskin

Parsons

et al. 1994

The Journal of Experimental Medicine

121

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SummaryCD40 plays an important role in B cell activation, proliferation, and Ig class switching. The signal transduction pathway mediated by CD40 was studied using monoclonal antibody (mAb) 626.1 to CD40. Burkitt's lymphoma and Epstein-Barr virus-transformed B cell lines and tonsilar B lymphocytes were treated with the anti-CD40 mAb for various lengths of time. The early events triggered by CD40 were examined by monitoring the changes in tyrosine phosphorylation of cellular proteins with anti-phosphotyrosine mAb. Dephosphorylation of specific proteins ranging between 50-110 kD and the appearance of a 28-kD tyrosine phosphorylated protein were seen within 30 s in human B cell lines. The dephosphorylation was reversed and the 28-kD protein was dephosphorylated in cells stimulated for 1 min. In resting B cells, the appearance of the 28-kD phosphoprotein was observed in 30 s after the addition of the anti-CD40 mAb. The tyrosine phosphorylation of this protein persisted. The patterns of protein tyrosine phosphorylation differed from those induced by an anti-immunoglobulin M mAb. The changes in the state of tyrosine phosphorylation induced by the anti-CD40 mAb were obviated by mAb to CD45, a protein tyrosine phosphatase (PTP) or by the addition of sodium orthovanadate, a broad PTP inhibitor. They were also blocked by protein tyrosine kinase (FFK) inhibitors, herbimycin A and genistein, and PKC and protein serine/threonine kinase inhibitors, H7 and HA1004. In addition, the alteration in the tyrosine phosphorylation ofPTKs Lyn, Fyn, and Syk was directly demonstrated. Engagement of CD40 for 30 s induced a transient decrease in tyrosine phosphorylation of these PTKs. These results indicate that the early events in CD40 signaling involve the complex interaction between PTP and protein kinases. C D40 is a 47-50-kD glycoprotein expressed on B cells and some normal and neoplastic epithelial cells including follicular dendritic cells and thymic epithelium (1-8). The cDNA sequences of both human and murine CD40 show that these glycoproteins are type I transmembrane proteins and contain cysteine-rich extracellular domains followed by serine/threonine-rich regions preceding the transmembrane domain (9, 10). They have significant homology to the members of the nerve growth factor receptor family (9-11).CD40 plays an important role in B cell activation, differentiation, and survival. Heterologous Abs and mAbs to CD40 induce B cell proliferation (1, 2, 4, 12, 13) and the engagement of CD40 by mAb provides a stimulatory signal synergistic with those delivered by IL-4 or Ab to either surface IgM (slgM) 1 or CD20 (2,14,15). An anti-CD40 mAb in the presence of IL-4 promotes long-term B cell growth (16). CD40 also plays a role in the induction of homotypic adhesion (17,18). A mAb to CD40 induces bcl-2 expression and Parts of these results have been presented in abstract form at the Annual Meeting AAP/ASCI/AFCR in

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“…sIgM have been extensively investigated (34,35,39,41,42). Our above results suggest that the early events of signal transduction mediated by CD40 differ from those mediated through sIg.…”

Section: Slgm-sediated Tyrosine Phosphorylatioa Differs From That Thrmentioning

confidence: 99%

“…Similar to slg, cross-linking of CD40 stimulates the phosphatidyl inositol pathway (34)(35)(36)(37). Unlike mAbs to IgM, the anti-CD40 mAb fails to stimulate a measurable increase in calcium influx in B cells (13).…”

mentioning

confidence: 99%

CD40 signaling pathway: anti-CD40 monoclonal antibody induces rapid dephosphorylation and phosphorylation of tyrosine-phosphorylated proteins including protein tyrosine kinase Lyn, Fyn, and Syk and the appearance of a 28-kD tyrosine phosphorylated protein.

Faris

Gaskin

Parsons

et al. 1994

The Journal of Experimental Medicine

121

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“…Immature B cells are more sensitive to Ag-induced tolerance than mature B cells (2). WEHI-231 B lymphoma cells serve as a cell line model of primary immature B cells, often used as a model system to analyze mIg-mediated tolerance (10,45). After the engagement of mIg, these cells undergo cell cycle arrest and eventual apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…These results suggest that Id3 plays a crucial role in mIg-mediated proliferative responses in mature B cells. In contrast, WEHI-231 cells, a model for primary immature B cells, underwent growth inhibition following the engagement of mIgs or the ectopic expression of Id3 (5,7,10) (Figs. 2, C and D, and 4B).…”

Section: Discussionmentioning

confidence: 99%

CD40 Ligand Rescues Inhibitor of Differentiation 3-Mediated G1 Arrest Induced by Anti-IgM in WEHI-231 B Lymphoma Cells

Hata

Yoshimoto

Mizuguchi

2004

The Journal of Immunology

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The engagement of membrane-bound Igs (mIgs) results in growth arrest, accompanied by apoptosis, in the WEHI-231 murine B lymphoma cells, a cell line model representative of primary immature B cells. Inhibitor of differentiation (Id) proteins, members of the helix-loop-helix protein family, functions in proliferation, differentiation, and apoptosis in a variety of cell types. In this study, we analyzed the involvement of Id protein in mIg-induced growth arrest and apoptosis in WEHI-231 cells. Following stimulation with anti-IgM, expression of Id3 was up-regulated at both the mRNA and protein levels; this up-regulation could be reversed by CD40L treatment. Retrovirus-mediated transduction of the Id3 gene into WEHI-231 cells resulted in an accumulation of the cells in G1 phase, but did not induce apoptosis. E box-binding activity decreased in response to anti-IgM administration, but increased after stimulation with either CD40L alone or anti-IgM plus CD40L, suggesting that E box-binding activity correlates with cell cycle progression. WEHI-231 cells overexpressing Id3 accumulated in G1 phase, which was accompanied by reduced levels of cyclin D2, cyclin E, and cyclin A, and a reciprocal up-regulation of p27Kip1. Both the helix-loop-helix and the C-terminal regions of Id3 were required for growth-suppressive activity. These data suggest that Id3 mimics mIg-mediated G1 arrest in WEHI-231 cells.

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“…Several lymphoma cell lines, including murine WEHI-231, are susceptible to apoptosis induction upon engagement of membrane immunoglobulin (mIg). These cell lines have been employed in studies of B cell unresponsiveness [6][7][8][9]. The induction of apoptosis in response to a range of apoptotic stimuli, including mIg engagement, is accompanied by modification of several intracellular signaling molecules, including hydrogen peroxide (H 2 O 2 ) [10], prolonged c-Jun N-terminal kinase (JNK) [7], Bcl-2 family proteins [11,12], and caspases [13].…”

Section: Introductionmentioning

confidence: 99%

Thy28 partially prevents apoptosis induction following engagement of membrane immunoglobulin in WEHI-231 B lymphoma cells

Toyota

Jiang

Asakura

et al. 2012

Cellular and Molecular Biology Letters

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Thy28 protein is conserved among plants, bacteria, and mammalian cells. Nuclear Thy28 protein is substantially expressed in testis, liver, and immune cells such as lymphocytes. Lymphocyte apoptosis plays a crucial role in homeostasis and formation of a diverse lymphocyte repertoire. In this study, we examined whether Thy28 affects induction of apoptosis in WEHI-231 B lymphoma cells following engagement of membrane immunoglobulin (mIg). Once they were established, the Thy28-overexpressing WEHI-231 cells showed similar expression levels of IgM and class I major histocompatibility complex (MHC) molecule compared with controls. The Thy28-overexpressing cells were considerably resistant to loss of mitochondrial membrane potential (ΔΨm), caspase-3 activation, and increase in annexin-positive cells upon mIg engagement. These changes were concomitant with an increase in G1 phase associated with upregulation of p27 Kip1 . The anti-IgM−induced sustained activation of c-Jun Nterminal kinase (JNK), which was associated with late-phase hydrogen peroxide (H 2 O 2 ) production, was partially reduced in the Thy28-expressing cells relative to controls. Taken together, the data suggest that in WEHI-231 B lymphoma cells, Thy28 regulates mIg-mediated apoptotic events through the JNK-H 2 O 2 activation pathway, concomitant with an accumulation of cells in G1 phase associated with upregulation of p27Kip1 in WEHI-231 B lymphoma cells.

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B‐Lymphocyte Signal Transduction in Response to Anti‐Immunoglobulin and Bacterial Lipopolysaccharide

Cited by 91 publications

References 62 publications

CD40 signaling pathway: anti-CD40 monoclonal antibody induces rapid dephosphorylation and phosphorylation of tyrosine-phosphorylated proteins including protein tyrosine kinase Lyn, Fyn, and Syk and the appearance of a 28-kD tyrosine phosphorylated protein.

CD40 signaling pathway: anti-CD40 monoclonal antibody induces rapid dephosphorylation and phosphorylation of tyrosine-phosphorylated proteins including protein tyrosine kinase Lyn, Fyn, and Syk and the appearance of a 28-kD tyrosine phosphorylated protein.

CD40 Ligand Rescues Inhibitor of Differentiation 3-Mediated G1 Arrest Induced by Anti-IgM in WEHI-231 B Lymphoma Cells

Thy28 partially prevents apoptosis induction following engagement of membrane immunoglobulin in WEHI-231 B lymphoma cells

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