Cutting Edge: A Threshold of B Cell Costimulatory Signals Is Required for Spontaneous Germinal Center Formation in Autoimmunity

2021 ◽  
pp. ji2100548
Author(s):  
Kristy Chiang ◽  
Andrea D. Largent ◽  
Tanvi Arkatkar ◽  
Christopher D. Thouvenel ◽  
Samuel W. Du ◽  
...  
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Cutting Edge ◽  
Costimulatory Signals ◽  
Germinal Center Formation

scholarly journals FBXO11 inactivation leads to abnormal germinal-center formation and lymphoproliferative disease

Blood ◽  
2016 ◽  
Vol 128 (5) ◽  
pp. 660-666 ◽  
Author(s):  
Christof Schneider ◽  
Ning Kon ◽  
Letizia Amadori ◽  
Qiong Shen ◽  
Friederike H. Schwartz ◽  
...  
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Cell Formation ◽  
Genetic Alterations ◽  
Lymphoproliferative Disease ◽  
Alternative Mechanism ◽  
Key Points ◽  
Bcl6 Expression ◽  
Germinal Center Formation

Key Points FBXO11 loss in mice enhances GC B-cell formation and leads to increased BCL6 expression. FBXO11 inactivation, mimicking genetic alterations identified in human lymphomas, represents an alternative mechanism of BCL6 deregulation.

scholarly journals Cutting Edge: Bcl6-Interacting Corepressor Contributes to Germinal Center T Follicular Helper Cell Formation and B Cell Helper Function

2015 ◽  
Vol 194 (12) ◽  
pp. 5604-5608 ◽  
Author(s):  
Jessica A. Yang ◽  
Noah J. Tubo ◽  
Micah D. Gearhart ◽  
Vivian J. Bardwell ◽  
Marc K. Jenkins
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Cell Formation ◽  
Cutting Edge ◽  
Helper Cell ◽  
Follicular Helper ◽  
Helper Function ◽  
T Follicular Helper Cell

scholarly journals gp39-CD40 interactions are essential for germinal center formation and the development of B cell memory.

1994 ◽  
Vol 180 (1) ◽  
pp. 157-163 ◽  
Author(s):  
T M Foy ◽  
J D Laman ◽  
J A Ledbetter ◽  
A Aruffo ◽  
E Claassen ◽  
...  
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Germinal Centers ◽  
Antibody Responses ◽  
Cell Memory ◽  
Specific Memory ◽  
B Cell Memory ◽  
Germinal Center Formation

gp39, the ligand for CD40 expressed on activated CD4+ T helper cells, is required for the generation of antibody responses to T-dependent (TD) antigens. Treatment of mice with anti-gp39 in vivo inhibits both primary and secondary antibody formation to TD, but not T-independent antigens. However, the role of this receptor-ligand pair in the development of germinal centers and the generation of B cell memory is as yet undefined. Using an antibody to gp39, this study examines the in vivo requirement for gp39-CD40 interactions in the induction of germinal center formation, as well as in the generation of B cell memory. Animals were immunized, treated in vivo with anti-gp39, and evaluated using immunohistochemical staining for the presence of splenic germinal centers 9-11 d after immunization. The results demonstrate that the formation of germinal centers was completely inhibited as a result of treatment with anti-gp39. Moreover, adoptive transfer experiments demonstrate that the generation of antigen-specific memory B cells is also inhibited as a consequence of blocking gp39-CD40 interactions. Taken together, the data demonstrate that gp39-CD40 interactions are critical not only for the generation of antibody responses, but also in the development of B cell memory.

Kinase MEKK1 is required for CD40-dependent activation of the kinases Jnk and p38, germinal center formation, B cell proliferation and antibody production

2006 ◽  
Vol 8 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Ewen Gallagher ◽  
Thomas Enzler ◽  
Atsushi Matsuzawa ◽  
Amy Anzelon-Mills ◽  
Dennis Otero ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
B Cell ◽  
Antibody Production ◽  
Germinal Center ◽  
Germinal Center Formation

scholarly journals Rap1 Is Essential for B-Cell Locomotion, Germinal Center Formation and Normal B-1a Cell Population

2021 ◽  
Vol 12 ◽  
Author(s):  
Sayaka Ishihara ◽  
Tsuyoshi Sato ◽  
Risa Sugioka ◽  
Ryota Miwa ◽  
Haruka Saito ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Specific Antibody ◽  
Stromal Cells ◽  
Germinal Center ◽  
Specific Antibody Production ◽  
Humoral Responses ◽  
Integrin Regulation ◽  
Germinal Center Formation

Integrin regulation by Rap1 is indispensable for lymphocyte recirculation. In mice having B-cell-specific Rap1a/b double knockouts (DKO), the number of B cells in lymph nodes decreased to approximately 4% of that of control mice, and B cells were present in the spleen and blood. Upon the immunization with NP-CGG, DKO mice demonstrated the defective GC formation in the spleen, and the reduced NP-specific antibody production. In vitro, Rap1 deficiency impaired the movement of activated B cells along the gradients of chemoattractants known to be critical for their localization in the follicles. Furthermore, B-1a cells were almost completely absent in the peritoneal cavity, spleen and blood of adult DKO mice, and the number of B-cell progenitor/precursor (B-p) were reduced in neonatal and fetal livers. However, DKO B-ps normally proliferated, and differentiated into IgM+ cells in the presence of IL-7. CXCL12-dependent migration of B-ps on the VCAM-1 was severely impaired by Rap1 deficiency. Immunostaining study of fetal livers revealed defects in the co-localization of DKO B-ps and IL-7-producing stromal cells. This study proposes that the profound effects of Rap1-deficiency on humoral responses and B-1a cell generation may be due to or in part caused by impairments of the chemoattractant-dependent positioning and the contact with stromal cells.

scholarly journals Brg1 Supports B Cell Proliferation and Germinal Center Formation Through Enhancer Activation

2021 ◽  
Vol 12 ◽  
Author(s):  
Dominik Schmiedel ◽  
Hadas Hezroni ◽  
Amit Hamburg ◽  
Ziv Shulman
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
B Cells ◽  
B Cell ◽  
Transcriptional Activation ◽  
Germinal Center ◽  
Cell Activation ◽  
Critical Role ◽  
B Cell Activation ◽  
Germinal Center Formation

Activation and differentiation of B cells depend on extensive rewiring of gene expression networks through changes in chromatin structure and accessibility. The chromatin remodeling complex BAF with its catalytic subunit Brg1 was previously identified as an essential regulator of early B cell development, however, how Brg1 orchestrates gene expression during mature B cell activation is less clear. Here, we find that Brg1 is required for B cell proliferation and germinal center formation through selective interactions with enhancers. Brg1 recruitment to enhancers following B cell activation was associated with increased chromatin accessibility and transcriptional activation of their coupled promoters, thereby regulating the expression of cell cycle-associated genes. Accordingly, Brg1-deficient B cells were unable to mount germinal center reactions and support the formation of class-switched plasma cells. Our findings show that changes in B cell transcriptomes that support B cell proliferation and GC formation depend on enhancer activation by Brg1. Thus, the BAF complex plays a critical role during the onset of the humoral immune response.

Sign in / Sign up

Export Citation Format

Share Document