scholarly journals Roles of the Tumor Suppressor p53 and the Cyclin-dependent Kinase Inhibitor p21WAF1/CIP1 in Receptor-mediated Apoptosis of WEHI 231 B Lymphoma Cells

1998 ◽  
Vol 187 (10) ◽  
pp. 1671-1679 ◽  
Author(s):  
Min Wu ◽  
Robert E. Bellas ◽  
Jian Shen ◽  
Gail E. Sonenshein
Keyword(s):  
Tumor Suppressor ◽  
B Cell ◽  
Kinase Inhibitor ◽  
Ectopic Expression ◽  
Cyclin Dependent Kinase ◽  
Lymphoma Cells ◽  
B Lymphoma ◽  
Cyclin Dependent Kinase Inhibitor ◽  
B Lymphoma Cells ◽  
Wehi 231

Treatment of WEHI 231 immature B lymphoma cells with an antibody against their surface immunoglobulin M (anti-IgM) induces apoptosis and has been studied extensively as a model of self-induced B cell tolerance. Since the tumor suppressor protein p53 has been implicated in apoptosis in a large number of cell types and has been found to be mutated in a variety of B cell tumors, here we sought to determine whether p53 and the p53 target gene cyclin-dependent kinase inhibitor p21WAF1/CIP1 were involved in anti-IgM–induced cell death. Anti-IgM treatment of WEHI 231 cells increased expression of p53 and p21 protein levels. Ectopic expression of wild-type p53 in WEHI 231 cells induced both p21 expression and apoptosis. Ectopic expression of p21 similarly induced apoptosis. Rescue of WEHI 231 cells from apoptosis by costimulation with CD40 ligand ablated the increase in p21 expression. Lastly, a significant decrease in anti-IgM–mediated apoptosis was seen upon downregulation of endogenous p53 activity by expression of a dominant-negative p53 protein or upon microinjection of an antisense p21 expression vector or antibody. Taken together, the above data demonstrate important roles for p53 and p21 proteins in receptor-mediated apoptosis of WEHI 231 B cells.

B cell receptor-induced growth arrest and apoptosis in WEHI-231 immature B lymphoma cells involve cyclic AMP and Epac proteins

2009 ◽  
Vol 21 (4) ◽  
pp. 609-621 ◽  
Author(s):  
Maria Grandoch ◽  
Maider López de Jesús ◽  
Paschal A. Oude Weernink ◽  
Artur-Aron Weber ◽  
Karl H. Jakobs ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
B Cell ◽  
Growth Arrest ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Lymphoma Cells ◽  
B Lymphoma ◽  
B Lymphoma Cells ◽  
Wehi 231

scholarly journals Lymphoma models for B cell activation and tolerance. III. Cell cycle dependence for negative signalling of WEHI-231 B lymphoma cells by anti-mu.

1986 ◽  
Vol 164 (1) ◽  
pp. 156-164 ◽  
Author(s):  
D W Scott ◽  
D Livnat ◽  
C A Pennell ◽  
P Keng
Keyword(s):  
Cell Cycle ◽  
B Cell ◽  
Cell Activation ◽  
S Phase ◽  
B Cell Activation ◽  
Lymphoma Cells ◽  
B Lymphoma ◽  
B Lymphoma Cells ◽  
Wehi 231 ◽  
G1 Cells

WEHI-231 B lymphoma cells have proven to be a useful model for the regulation of growth of normal B cells by anti-Ig reagents. We previously reported that the growth of these lymphoma cells is inhibited by heterologous or monoclonal anti-mu or anti-kappa reagents. Such cells cease to incorporate thymidine within 24-48 h of exposure to anti-Ig reagents, but are not adversely affected by antibodies directed at either class I or class II histocompatibility antigens. In fact, cell cycle analysis revealed that anti-mu causes a block in the transition of these cells from G1 to S phase. To further study the mechanism of growth inhibition, we have purified lymphoma cells in G1 by centrifugal elutriation, or enriched WEHI-231 cells at the G1/S interface by treatment with hydroxyurea, and followed their progression through the cell cycle in the presence or absence of anti-mu. Our data show that WEHI-231 B lymphoma cells receive a negative signal early in G1, since delayed addition of anti-mu (to late G1 cells) leads to no alteration in cell cycle progression at 24 h, and exposure to anti-mu during S does not alter progress through DNA synthesis and mitosis. Moreover, exposure to anti-mu for only 2 h prevents purified G1 cells from entering their first S phase. The nature of the relevant processes in early G1 is discussed in terms of models of B cell activation and tolerance induction.

The role of bcl-xL in CD40-mediated rescue from anti-μ-induced apoptosis in WEHI-231 B lymphoma cells

1995 ◽  
Vol 25 (5) ◽  
pp. 1352-1357 ◽  
Author(s):  
Michael S. K. Choi ◽  
Lawrence H. Boise ◽  
Alexander R. Gottschalk ◽  
José Quintans ◽  
Craig B. Thompson ◽  
...  
Keyword(s):  
Lymphoma Cells ◽  
B Lymphoma ◽  
B Lymphoma Cells ◽  
Wehi 231 ◽  
Induced Apoptosis

Functional Loss of p21/Waf-1 in a Case of Benign Canine Multicentric Melanoma

1998 ◽  
Vol 35 (2) ◽  
pp. 94-101 ◽  
Author(s):  
M. G. Ritt ◽  
J. Wojcieszyn ◽  
J. F. Modiano
Keyword(s):  
Tumor Suppressor ◽  
Cell Cycle Progression ◽  
Kinase Inhibitor ◽  
P53 Gene ◽  
Tumor Formation ◽  
Cyclin Dependent Kinase ◽  
P53 Expression ◽  
Functional Loss ◽  
Normal Tissues ◽  
Cyclin Dependent Kinase Inhibitor

Mutations of tumor suppressor genes remove mechanisms that normally arrest proliferation of transformed cells, resulting in tumor formation. The p53 gene product functions as a tumor suppressor that induces p21/Waf-1, the 21-kDa product of the waf-1/cip-1/mda-6 gene. p21/Waf-1 is a pan-cyclin-dependent kinase inhibitor that arrests cell cycle progression under a variety of circumstances. We examined tissues from a dog with multiple primary pigmented proliferative lesions (benign, multicentric melanoma consisting of three distinct dermal lesions and a matrical cyst) for p21/Waf-1 and p53 expression by immunohistochemistry and immunoblotting. p21/Waf-1 and p-53 proteins were undetectable in the tumor cells and in the cyst but were present in adjacent normal tissues. Abundant cyclin-dependent kinase 4 (Cdk4), a protein related functionally to p21/Waf-1, also was present in the cyst. A somatic mutation of the waf-1 gene or of the p53 gene may have resulted in the loss of p21/Waf-1 expression in a common precursor of pigment-producing cells from the affected dog. Furthermore, this functional loss of p21/Waf-1 may play an important role in the genesis of canine benign melanoma.

scholarly journals Antigen-armed antibodies targeting B lymphoma cells effectively activate antigen-specific CD4+ T cells

Blood ◽  
2015 ◽  
Vol 125 (10) ◽  
pp. 1601-1610 ◽  
Author(s):  
Xiaojun Yu ◽  
Marta Ilecka ◽  
Emmalene J. Bartlett ◽  
Viktor Schneidt ◽  
Rauf Bhat ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Cd4 T Cells ◽  
Memory T Cells ◽  
Ex Vivo ◽  
B Cell Receptors ◽  
Lymphoma Cells ◽  
B Lymphoma ◽  
B Lymphoma Cells ◽  
Key Points

Key PointsEpitopes in antigen-armed antibodies that target B-cell receptors are efficiently presented by B lymphoma cells to cytotoxic CD4+ T cells. Memory T cells activated by AgAbs ex vivo are able to kill targeted B lymphoma cells.

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