scholarly journals Compartments and Connections Within the Germinal Center

2021 ◽  
Vol 12 ◽  
Author(s):  
Domenick E. Kennedy ◽  
Marcus R. Clark
Keyword(s):  
Germinal Center ◽  
Recent Progress ◽  
Cell Function ◽  
Developmental Process ◽  
Antibody Responses ◽  
High Affinity ◽  
B Cell Function ◽  
Distinct Cell ◽  
Function Selection ◽  
Evolution Of Immunity

Protective high affinity antibody responses emerge through an orchestrated developmental process that occurs in germinal centers (GCs). While GCs have been appreciated since 1930, a wealth of recent progress provides new insights into the molecular and cellular dynamics governing humoral immunity. In this review, we highlight advances that demonstrate that fundamental GC B cell function, selection, proliferation and SHM occur within distinct cell states. The resulting new model provides new opportunities to understand the evolution of immunity in infectious, autoimmune and neoplastic diseases.

scholarly journals Downregulation of FOXP1 is required during germinal center B-cell function

Blood ◽  
2013 ◽  
Vol 121 (21) ◽  
pp. 4311-4320 ◽  
Author(s):  
Ainara Sagardoy ◽  
Jose I. Martinez-Ferrandis ◽  
Sergio Roa ◽  
Karen L. Bunting ◽  
María Angela Aznar ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
B Cell ◽  
Germinal Center ◽  
Cell Function ◽  
Germinal Centers ◽  
B Cell Function ◽  
Germinal Center B Cell ◽  
Key Points ◽  
And Function

Key Points FOXP1 is downregulated in germinal centers, inversely to BCL6, whereby it regulates a network of genes, half of which are also BCL6 targets. In transgenic mice, constitutive FOXP1 expression impairs GC formation and function, which might contribute to B-cell lymphomagenesis.

scholarly journals Metformin Enhances B Cell Function and Antibody Responses of Elderly Individuals With Type-2 Diabetes Mellitus

2021 ◽  
Vol 2 ◽  
Author(s):  
Daniela Frasca ◽  
Alain Diaz ◽  
Maria Romero ◽  
Bonnie B. Blomberg
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
B Cells ◽  
Influenza Vaccine ◽  
B Cell ◽  
Cell Function ◽  
Antibody Responses ◽  
B Cell Function

Our previous work has shown that young and elderly patients with Type-2 Diabetes Mellitus (T2DM) treated with Metformin have optimal B cell function and serum antibodies specific for the seasonal influenza vaccine. In this paper, we have evaluated B cell function and the metabolic requirements of B cell antibody responses in elderly T2DM patients (ET2DM) taking or not Metformin, and compared to those of healthy elderly (EH) and healthy young (YH) individuals. Results show that Metformin significantly increases in vivo B cell function, measured by influenza vaccine-specific serum antibodies, in ET2DM patients to the levels observed in EH and more importantly in YH individuals. Metformin also decreases the frequencies of pro-inflammatory B cell subsets, as well as intrinsic inflammation and metabolic requirements of peripheral B cells from ET2DM. This hyper-metabolic phenotype of B cells from ET2DM is needed to support intrinsic inflammation, measured by the expression of transcripts for markers of the senescence-associated secretory phenotype (SASP), and the secretion of autoimmune antibodies. Importantly, B cell function in ET2DM patients taking Metformin is not only increased as compared to that in ET2DM patients not taking Metformin, but is comparable to B cell function measured in YH individuals. These results altogether strongly support the anti-aging effects of Metformin on humoral immunity.

scholarly journals Impaired B cell function during viral infections due to PTEN-mediated inhibition of the PI3K pathway

2017 ◽  
Vol 214 (4) ◽  
pp. 931-941 ◽  
Author(s):  
Andrew Getahun ◽  
Scott M. Wemlinger ◽  
Pratyaydipta Rudra ◽  
Mario L. Santiago ◽  
Linda F. van Dyk ◽  
...  
Keyword(s):  
B Cells ◽  
Viral Infection ◽  
B Cell ◽  
Cell Function ◽  
Pi3k Pathway ◽  
Antibody Responses ◽  
Common Mechanism ◽  
Lymphocyte Migration ◽  
B Cell Function ◽  
Acute Viral Infection

Transient suppression of B cell function often accompanies acute viral infection. However, the molecular signaling circuitry that enforces this hyporesponsiveness is undefined. In this study, experiments identify up-regulation of the inositol phosphatase PTEN (phosphatase and tensin homolog) as primarily responsible for defects in B lymphocyte migration and antibody responses that accompany acute viral infection. B cells from mice acutely infected with gammaherpesvirus 68 are defective in BCR- and CXCR4-mediated activation of the PI3K pathway, and this, we show, is associated with increased PTEN expression. This viral infection-induced PTEN overexpression appears responsible for the suppression of antibody responses observed in infected mice because PTEN deficiency or expression of a constitutively active PI3K rescued function of B cells in infected mice. Conversely, induced overexpression of PTEN in B cells in uninfected mice led to suppression of antibody responses. Finally, we demonstrate that PTEN up-regulation is a common mechanism by which infection induces suppression of antibody responses. Collectively, these findings identify a novel role for PTEN during infection and identify regulation of the PI3K pathway, a mechanism previously shown to silence autoreactive B cells, as a key physiological target to control antibody responses.

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