Project description:Trancriptional comparison of Zbtb32-deficient and -sufficient NP-specific memory B cells at day 7 of recall response [memory B cells]
Project description:Memory B cell responses are more rapid and of greater magnitude than are primary antibody responses. The mechanisms by which these secondary responses are eventually attenuated remain unknown. We demonstrate that the transcription factor ZBTB32 limits the rapidity and duration of antibody recall responses. ZBTB32 is highly expressed by mouse and human memory B cells, but not by their naïve counterparts. Zbtb32-/- mice mount normal primary antibody responses to T-dependent antigens. However, Zbtb32-/- memory B cell-mediated recall responses occur more rapidly and persist longer than do control responses. Microarray analyses demonstrate that Zbtb32-/- secondary bone marrow plasma cells display elevated expression of genes that promote cell cycle progression and mitochondrial function relative to wild-type controls. BrdU labeling and adoptive transfer experiments confirm more rapid production and a cell-intrinsic survival advantage of Zbtb32-/- secondary plasma cells relative to wild-type counterparts. ZBTB32 is therefore a novel negative regulator of antibody recall responses. Wild type and Zbtb32-/- resting polyclonal splenic memory B cells were purified by fluorescence activated cell sorting, RNA was extracted, and used for Affymetrix microarray analysis. 5 biological replicates of wild type and Zbtb32-/- cells were included for each cell type.
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
Project description:Memory B cell responses are more rapid and of greater magnitude than are primary antibody responses. The mechanisms by which these secondary responses are eventually attenuated remain unknown. We demonstrate that the transcription factor ZBTB32 limits the rapidity and duration of antibody recall responses. ZBTB32 is highly expressed by mouse and human memory B cells, but not by their naïve counterparts. Zbtb32-/- mice mount normal primary antibody responses to T-dependent antigens. However, Zbtb32-/- memory B cell-mediated recall responses occur more rapidly and persist longer than do control responses. Microarray analyses demonstrate that Zbtb32-/- secondary bone marrow plasma cells display elevated expression of genes that promote cell cycle progression and mitochondrial function relative to wild-type controls. BrdU labeling and adoptive transfer experiments confirm more rapid production and a cell-intrinsic survival advantage of Zbtb32-/- secondary plasma cells relative to wild-type counterparts. ZBTB32 is therefore a novel negative regulator of antibody recall responses. CD45.2 wild type and Zbtb32-/- splenocytes from NP-CGG-immune donors were transferred into CD45.1 recipients and challenged with NP-CGG. CD45.2 donor NP-specific memory B cells were isolated from the spleen 7 days later. 5-6 biological replicates of each genotype were performed.
Project description:Memory B cell responses are more rapid and of greater magnitude than are primary antibody responses. The mechanisms by which these secondary responses are eventually attenuated remain unknown. We demonstrate that the transcription factor ZBTB32 limits the rapidity and duration of antibody recall responses. ZBTB32 is highly expressed by mouse and human memory B cells, but not by their naïve counterparts. Zbtb32-/- mice mount normal primary antibody responses to T-dependent antigens. However, Zbtb32-/- memory B cell-mediated recall responses occur more rapidly and persist longer than do control responses. Microarray analyses demonstrate that Zbtb32-/- secondary bone marrow plasma cells display elevated expression of genes that promote cell cycle progression and mitochondrial function relative to wild-type controls. BrdU labeling and adoptive transfer experiments confirm more rapid production and a cell-intrinsic survival advantage of Zbtb32-/- secondary plasma cells relative to wild-type counterparts. ZBTB32 is therefore a novel negative regulator of antibody recall responses.