Analysis Tools
immune system
|
• germinal center B cells sorted from Peyer's patches of aged mice show a significantly lower mutation frequency at both JH4 and JK5 intronic regions, with a higher proportion of sequences harboring zero or less than 5 mutations and a concomitant decrease in the number of highly mutated clones relative to control mice
|
|
• mice show a marked reduction in the number of splenic resting mature B cells
|
|
• unimmunized mice show a reduced percentage of germinal center B cells (and IgA+ germinal center cells) in Peyer's patches
|
|
• activated B cells exhibit sustained expression of the integrated stress response (ISR) effector activating transcription factor 4 (Atf4) and induction of the ISR transcriptional program, increased cell death, and reduced AID (activation-induced cytidine deaminase) expression relative to control cells
• resting B cells show phosphorylation of Perk and its downstream target eIF2alpha as well as Atf4 expression, indicating constitutive activation of the Perk-mediated ISR pathway
• however, plasma cell differentiation and function are normal under steady-state conditions
|
|
• CaspGLOW staining of cultured splenocytes revealed increased caspase activity at 24 and 48 h after activation with LPS + IL-4 or LPS-BAFF-TGFbeta
• number of live cells in splenocyte cultures is significantly decreased at 48 and 72 h after activation with LPS + IL-4
|
|
• primary splenic B cells show lower levels of class switch recombination (CSR) for all tested isotypes under in vitro conditions that induce switching to IgG1, IgG3, IgG2b or IgA
• CSR defect is due to impaired formation of AID-induced DNA double-strand breaks (DSBs), caused by defective induction of AID expression with further contribution of impaired germline transcription (GLT) in an isotype-specific manner
• percentage of switched IgA germinal center B cells is significantly reduced in Peyer's patches
• however, B cell proliferation is normal under all stimulation conditions, and class switching is reduced independently of the number of cell divisions
|
cellular
|
• CaspGLOW staining of cultured splenocytes revealed increased caspase activity at 24 and 48 h after activation with LPS + IL-4 or LPS-BAFF-TGFbeta
• number of live cells in splenocyte cultures is significantly decreased at 48 and 72 h after activation with LPS + IL-4
|
|
• splenocyte cultures show an increased proportion of cells with low mitochondrial membrane potential at 24 and 48 h after activation with LPS + IL-4
• however, no changes are observed in mitochondrial mass or respiration capacity
|
hematopoietic system
|
• germinal center B cells sorted from Peyer's patches of aged mice show a significantly lower mutation frequency at both JH4 and JK5 intronic regions, with a higher proportion of sequences harboring zero or less than 5 mutations and a concomitant decrease in the number of highly mutated clones relative to control mice
|
|
• mice show a marked reduction in the number of splenic resting mature B cells
|
|
• unimmunized mice show a reduced percentage of germinal center B cells (and IgA+ germinal center cells) in Peyer's patches
|
|
• activated B cells exhibit sustained expression of the integrated stress response (ISR) effector activating transcription factor 4 (Atf4) and induction of the ISR transcriptional program, increased cell death, and reduced AID (activation-induced cytidine deaminase) expression relative to control cells
• resting B cells show phosphorylation of Perk and its downstream target eIF2alpha as well as Atf4 expression, indicating constitutive activation of the Perk-mediated ISR pathway
• however, plasma cell differentiation and function are normal under steady-state conditions
|
|
• CaspGLOW staining of cultured splenocytes revealed increased caspase activity at 24 and 48 h after activation with LPS + IL-4 or LPS-BAFF-TGFbeta
• number of live cells in splenocyte cultures is significantly decreased at 48 and 72 h after activation with LPS + IL-4
|
|
• primary splenic B cells show lower levels of class switch recombination (CSR) for all tested isotypes under in vitro conditions that induce switching to IgG1, IgG3, IgG2b or IgA
• CSR defect is due to impaired formation of AID-induced DNA double-strand breaks (DSBs), caused by defective induction of AID expression with further contribution of impaired germline transcription (GLT) in an isotype-specific manner
• percentage of switched IgA germinal center B cells is significantly reduced in Peyer's patches
• however, B cell proliferation is normal under all stimulation conditions, and class switching is reduced independently of the number of cell divisions
|
