Patricia J. Gearhart, Ph.D.
Laboratory of Molecular Biology and Immunology
251 Bayview Boulevard
Baltimore, MD 21224
AID and Somatic Hypermutation: Somatic hypermutation of immunoglobulin genes occurs at a frequency that is a million times greater than mutation in other genes. Mutations are found in both variable genes and switch regions before constant genes. We have used biochemical and genetic techniques to study this fascinating process that occurs constantly in every B lymphocyte in the human body. Hypermutation is initiated when the activation-induced deaminase (AID) protein deaminates cytosine in DNA to uracil.
Dr. Patricia Gearhart received her Ph.D. in immunology from the University of Pennsylvania in 1974. She performed postdoctoral training at the Johns Hopkins University and was a staff associate at the Carnegie Institution of Washington until 1982. She then became a faculty member at the Johns Hopkins University until 1995, when she moved to the NIA.
Pape KA, Maul RW, Dileepan T, Paustian AS, Gearhart PJ, Jenkins MK. Naive B Cells with High-Avidity Germline-Encoded Antigen Receptors Produce Persistent IgM<sup>+</sup> and Transient IgG<sup>+</sup> Memory B Cells. Immunity. 2018;48(6):1135-1143.e4.
Russell Knode LM, Naradikian MS, Myles A, Scholz JL, Hao Y, Liu D, Ford ML, Tobias JW, Cancro MP, Gearhart PJ. Age-Associated B Cells Express a Diverse Repertoire of V<sub>H</sub> and Vκ Genes with Somatic Hypermutation. J Immunol. 2017;198(5):1921-1927.
Maul RW, Cao Z, Venkataraman L, Giorgetti CA, Press JL, Denizot Y, Du H, Sen R, Gearhart PJ. Spt5 accumulation at variable genes distinguishes somatic hypermutation in germinal center B cells from ex vivo-activated cells. J Exp Med. 2014;211(11):2297-306.
Maul RW, MacCarthy T, Frank EG, Donigan KA, McLenigan MP, Yang W, Saribasak H, Huston DE, Lange SS, Woodgate R, Gearhart PJ. DNA polymerase ι functions in the generation of tandem mutations during somatic hypermutation of antibody genes. J Exp Med. 2016;213(9):1675-83.
Castiblanco DP, Maul RW, Russell Knode LM, Gearhart PJ. Co-Stimulation of BCR and Toll-Like Receptor 7 Increases Somatic Hypermutation, Memory B Cell Formation, and Secondary Antibody Response to Protein Antigen. Front Immunol. 2017;8:1833.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
This page was last updated on August 14th, 2018