Publications by authors named "Jessica J McDonald"
Article Synopsis
- Somatic hypermutation (SHM) enhances the diversity of antibody (Ab) genes in activated B cells, leading to antibodies with higher affinity for antigens (Ag).
- Enhancers known as diversification activators (DIVACs) are responsible for targeting SHM to immunoglobulin (Ig) genes, but their specific mechanisms were unclear until now.
- In experiments with chicken DT40 B cells and human Ramos Burkitt lymphoma cells, it was found that DIVACs increase the phosphorylation and occupancy of RNA polymerase II (Pol II) in target genes, causing stalling without enhancing full-length transcript production, thereby enabling mutation without necessitating increased transcription.
Article Synopsis
- - Somatic hypermutation (SH) occurs in activated B cells and introduces point mutations in immunoglobulin (Ig) genes, enhancing antibody diversity for better affinity maturation.
- - The study reveals that Ig enhancers significantly promote SH in adjacent genes, despite not noticeably increasing transcription, and certain mutations in key regulatory binding sites hinder this activation.
- - The findings point to a new role for Ig enhancers in recruiting the AID protein or modifying nearby transcription units, and this mechanism appears to be conserved across species, as seen in both mammals and chickens.
Article Synopsis
- Secondary B cell diversification happens through somatic hypermutation (SHM) in germinal centers after antigen stimulation, enhancing antibody affinity.
- The study identifies the importance of "E boxes," specific DNA sequences, in SHM targeting, with experiments showing that mutating these elements drastically reduces SHM activity.
- Results emphasize that while E boxes are crucial for SHM, they rely on their surrounding sequences to function effectively, highlighting a complex interaction in determining SHM targeting to immunoglobulin loci.
Article Synopsis
- Somatic hypermutation (SHM) enhances the diversity of immunoglobulin (Ig) genes, leading to the selection of B cells that produce high-affinity antibodies through a process called affinity maturation.
- SHM is initiated in activated B cells by the enzyme activation-induced deaminase (AID), which induces mutations primarily at Ig loci, although misdirected SHM can cause DNA damage elsewhere.
- Research using a reporter system in chicken B cells identified a 1.9-kb DIVAC element from chicken IgL that significantly boosts AID-dependent mutation, revealing critical regions for its function and suggesting that multiple DNA elements work together to recruit the mutational machinery at Ig gene regions.
