Synergistic roles of DYRK1A and GATA1 in trisomy 21 megakaryopoiesis.

Patients with Down syndrome (DS), or trisomy 21 (T21), are at increased risk of transient abnormal myelopoiesis (TAM) and acute megakaryoblastic leukemia (ML-DS). Both TAM and ML-DS require prenatal somatic mutations in GATA1, resulting in the truncated isoform GATA1s. The mechanism by which individual chromosome 21 (HSA21) genes synergize with GATA1s for leukemic transformation is challenging to study, in part due to limited human cell models with wild-type GATA1 (wtGATA1) or GATA1s.

The IgH -MAR regions promote UNG-dependent error-prone repair to optimize somatic hypermutation.

Intoduction: Two scaffold/matrix attachment regions (5'- and 3'- ) flank the intronic core enhancer (c) within the immunoglobulin heavy chain locus (). Besides their conservation in mice and humans, the physiological role of is still unclear and their involvement in somatic hypermutation (SHM) has never been deeply evaluated.

Methods: Our study analyzed SHM and its transcriptional control in a mouse model devoid of , further combined to relevant models deficient for base excision repair and mismatch repair.

Antibodies in action: the role of humoral immunity in the fight against atherosclerosis.

The sequestering of oxidation-modified low-density lipoprotein by macrophages results in the accumulation of fatty deposits within the walls of arteries. Necrosis of these cells causes a release of intercellular epitopes and the activation of the adaptive immune system, which we predict leads to robust autoantibody production. T cells produce cytokines that act in the plaque environment and further stimulate B cell antibody production.

Greater Breadth of Vaccine-Induced Immunity in Females than Males Is Mediated by Increased Antibody Diversity in Germinal Center B Cells.

Inactivated influenza vaccines induce greater antibody responses in females than males among both humans and mice. To test the breadth of protection, we used recombinant mouse-adapted A/California/2009 (maA/Cal/09) H1N1 viruses containing mutations at one (1M), two (2M), or three (3M) antigenic sites, in addition to a virus containing the 1M mutation and a substitution of the Ca2 antigenic site (Sub) with one derived from an H5 hemagglutinin (HA) to challenge mice of both sexes. Following maA/Cal/09 vaccination, females produced greater virus-specific, class-switched total IgG and IgG2c antibodies against the vaccine and all mutant viruses, and antibodies from females recognized a greater number of unique, linear HA epitopes than did antibodies from males.