scholarly journals B Cell Development sans B Cell Receptor Responsiveness Due to Unfolded Protein Response–Triggered Mef2c Protein Degradation

2018 ◽  
Vol 201 (10) ◽  
pp. 2885-2898 ◽  
Author(s):  
Yi-Ting Chen ◽  
Yu-Chia Su ◽  
John T. Kung
2005 ◽  
Vol 280 (48) ◽  
pp. 39762-39771 ◽  
Author(s):  
Alison H. Skalet ◽  
Jennifer A. Isler ◽  
Leslie B. King ◽  
Heather P. Harding ◽  
David Ron ◽  
...  

1998 ◽  
Vol 20 (4) ◽  
pp. 383
Author(s):  
S. R. Rheingold ◽  
M. Jiang ◽  
S. A. Grupp ◽  
B. Himelstein

2006 ◽  
Vol 26 (24) ◽  
pp. 9364-9376 ◽  
Author(s):  
Renren Wen ◽  
Yuhong Chen ◽  
Li Bai ◽  
Guoping Fu ◽  
James Schuman ◽  
...  

ABSTRACT Phospholipase Cγ2 (PLCγ2) is a critical signaling effector of the B-cell receptor (BCR). Here we show that PLCγ2 deficiency impedes early B-cell development, resulting in an increase of B220+ CD43+ BP-1+ CD24hi pre-BCR+ large pre-B cells. PLCγ2 deficiency impairs pre-BCR-mediated functions, leading to enhanced interleukin-7 (IL-7) signaling and elevated levels of RAGs in the selected large pre-B cells. Consequently, PLCγ2 deficiency renders large pre-B cells susceptible to transformation, resulting in dramatic acceleration of Myc-induced lymphomagenesis. PLCγ2 −/− Eμ-Myc transgenic mice mainly develop lymphomas of B220+ CD43+ BP-1+ CD24hi pre-BCR+ large pre-B-cell origin, which are uncommon in wild-type Eμ-Myc transgenics. Furthermore, lymphomas from PLCγ2 −/− Eμ-Myc transgenic mice exhibited a loss of p27Kip1 and often displayed alterations in Arf or p53. Thus, PLCγ2 plays an important role in pre-BCR-mediated early B-cell development, and its deficiency leads to markedly increased pools of the most at-risk large pre-B cells, which display hyperresponsiveness to IL-7 and express high levels of RAGs, making them prone to secondary mutations and Myc-induced malignancy.


2021 ◽  
Vol 12 ◽  
Author(s):  
Alec J. Wishnie ◽  
Tzippora Chwat-Edelstein ◽  
Mary Attaway ◽  
Bao Q. Vuong

B cells produce high-affinity immunoglobulins (Igs), or antibodies, to eliminate foreign pathogens. Mature, naïve B cells expressing an antigen-specific cell surface Ig, or B cell receptor (BCR), are directed toward either an extrafollicular (EF) or germinal center (GC) response upon antigen binding. B cell interactions with CD4+ pre-T follicular helper (pre-Tfh) cells at the T-B border and effector Tfh cells in the B cell follicle and GC control B cell development in response to antigen. Here, we review recent studies demonstrating the role of B cell receptor (BCR) affinity in modulating T-B interactions and the subsequent differentiation of B cells in the EF and GC response. Overall, these studies demonstrate that B cells expressing high affinity BCRs preferentially differentiate into antibody secreting cells (ASCs) while those expressing low affinity BCRs undergo further affinity maturation or differentiate into memory B cells (MBCs).


Immunity ◽  
1998 ◽  
Vol 9 (3) ◽  
pp. 405-411 ◽  
Author(s):  
Robert G Caldwell ◽  
Joanna B Wilson ◽  
Steven J Anderson ◽  
Richard Longnecker

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