cellular
• B cells stimulated in vitro in the presence of LPS or LPS + IL-4 have reduced cellular proliferation compared to controls
• viability of stimulated cells drops dramatically three days after stimulation
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• B cells undergoing class switch recombination have a 4-fold greater frequency of irregular chromosomes (broken chromosomes, chromosome fusions, and translocations) than controls
• many of these chromosome breaks occur at the IgH locus
• when B cells are activated without class switch recombination, there is still an increased frequency of chromosome breaks but none occur at the IgH locus
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immune system
• B cells stimulated in vitro in the presence of LPS or LPS + IL-4 have reduced cellular proliferation compared to controls
• viability of stimulated cells drops dramatically three days after stimulation
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• there is a 2-3 fold reduced frequency of B cells that switch to IgG3 or IgG1 when stimulated in vitro in the presence of LPS or LPS + IL-4, respectively, as compared to controls
• this reduced class switch recombination is still observed when comparisons are made between B cells that have undergone the same number of divisions
• S-mu switch regions have less somatic mutations than controls due to mutant cells having less opportunity to accumulate mutations before switching
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• the percentage of mutations that occur in the recombined IgH locus of germinal center B cells is roughly half that of controls
• the mutation percentage drops to less than a third of controls when germinal center B cells are pre-screened to keep only those that have excised the floxed allele
• almost 50% of all sequences derived from these cells contained only one mutation, whereas close to 80% of the sequences derived from controls had multiple mutations
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• there is a 2-3 fold reduction in the number of germinal center B cells
• this population is slightly enriched for cells that have escaped cre-mediated deletion of the floxed allele
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• sera levels of antigen-specific IgG1 and Iglambda are half that of controls after immunization
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hematopoietic system
• B cells stimulated in vitro in the presence of LPS or LPS + IL-4 have reduced cellular proliferation compared to controls
• viability of stimulated cells drops dramatically three days after stimulation
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• there is a 2-3 fold reduced frequency of B cells that switch to IgG3 or IgG1 when stimulated in vitro in the presence of LPS or LPS + IL-4, respectively, as compared to controls
• this reduced class switch recombination is still observed when comparisons are made between B cells that have undergone the same number of divisions
• S-mu switch regions have less somatic mutations than controls due to mutant cells having less opportunity to accumulate mutations before switching
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• the percentage of mutations that occur in the recombined IgH locus of germinal center B cells is roughly half that of controls
• the mutation percentage drops to less than a third of controls when germinal center B cells are pre-screened to keep only those that have excised the floxed allele
• almost 50% of all sequences derived from these cells contained only one mutation, whereas close to 80% of the sequences derived from controls had multiple mutations
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• there is a 2-3 fold reduction in the number of germinal center B cells
• this population is slightly enriched for cells that have escaped cre-mediated deletion of the floxed allele
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• sera levels of antigen-specific IgG1 and Iglambda are half that of controls after immunization
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