We will see if ABCs have encountered antigen and undergone somatic hypermutation and class switching. Diversity in the repertoire and the mutation frequency will be examined in old mice. This may determine if the old cells are exhausted from chronic antigen exposure. To determine what antigens induce non-responsive B cells, we will sequence heavy and light chains from single cells, clone them into expression vectors, and test for reactivity to a panel of antigens. To see if ABCs prevent affinity maturation of follicular cells, we will transfer cells into recipient mice, immunize, and measure affinity.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000777-02
Application #
8736625
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2013
Total Cost
$723,256
Indirect Cost
Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
Zip Code
Russell Knode, Lisa M; Naradikian, Martin S; Myles, Arpita et al. (2017) Age-Associated B Cells Express a Diverse Repertoire of VH and V? Genes with Somatic Hypermutation. J Immunol 198:1921-1927
Myles, Arpita; Gearhart, Patricia J; Cancro, Michael P (2017) Signals that drive T-bet expression in B cells. Cell Immunol 321:3-7
Jones, Bart G; Penkert, Rhiannon R; Xu, Beisi et al. (2016) Binding of estrogen receptors to switch sites and regulatory elements in the immunoglobulin heavy chain locus of activated B cells suggests a direct influence of estrogen on antibody expression. Mol Immunol 77:97-102
Hurwitz, Julia L; Penkert, Rhiannon R; Xu, Beisi et al. (2016) Hotspots for Vitamin-Steroid-Thyroid Hormone Response Elements Within Switch Regions of Immunoglobulin Heavy Chain Loci Predict a Direct Influence of Vitamins and Hormones on B Cell Class Switch Recombination. Viral Immunol 29:132-6
Vallabhaneni, Haritha; Zhou, Fang; Maul, Robert W et al. (2015) Defective repair of uracil causes telomere defects in mouse hematopoietic cells. J Biol Chem 290:5502-11
Maul, Robert W; Gearhart, Patricia J (2014) Refining the Neuberger model: Uracil processing by activated B cells. Eur J Immunol 44:1913-6