The overall goal of the collaborative project is to develop predictive computational models for antibody affinity maturation. This component (Project 3) will contribute the molecular characterization of antibodies and antigens that will be needed to calibrate and test the computational predictions. The experimental work proposed here is based on B-cell lineage analysis, which enables a reconstruction of the history of mutations at the Ig-encoding locus during the trajectory from a naive response to an evolved antibody. Structural and biophysical characterization of the progenitor antibody of a lineage and of its clonal descendants, including the intermediates in the genealogy, provide information about both the output from any stage in the evolution from progenitor to mature antibody and the input to any subsequent stage. These data are essential for any realistic model of affinity maturation and for relating cellular and molecular interactions in a germinal center to their functional consequences. We will produce recombinant influenza virus hemagglutinin (HA) trimeric ectodomain and anthrax toxin protective antigen (PA) as immunogens, analyze the results of those immunizations produced in Project 2, and generate recombinant Fab fragments (chosen because of the characteristics of the lineage from which they derive) for structural and biophysical studies.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Boston University
United States
Zip Code
Finney, Joel; Yeh, Chen-Hao; Kelsoe, Garnett et al. (2018) Germinal center responses to complex antigens. Immunol Rev 284:42-50
McCarthy, Kevin R; Watanabe, Akiko; Kuraoka, Masayuki et al. (2018) Memory B Cells that Cross-React with Group 1 and Group 2 Influenza A Viruses Are Abundant in Adult Human Repertoires. Immunity 48:174-184.e9
Kelsoe, Garnett; Haynes, Barton F (2018) What Are the Primary Limitations in B-Cell Affinity Maturation, and How Much Affinity Maturation Can We Drive with Vaccination? Breaking through Immunity's Glass Ceiling. Cold Spring Harb Perspect Biol 10:
Finney, Joel; Kelsoe, Garnett (2018) Poly- and autoreactivity of HIV-1 bNAbs: implications for vaccine design. Retrovirology 15:53
Takahashi, Yoshimasa; Kelsoe, Garnett (2017) Role of germinal centers for the induction of broadly-reactive memory B cells. Curr Opin Immunol 45:119-125
Wheaton, Joshua D; Yeh, Chen-Hao; Ciofani, Maria (2017) Cutting Edge: c-Maf Is Required for Regulatory T Cells To Adopt ROR?t+ and Follicular Phenotypes. J Immunol 199:3931-3936
Kuraoka, Masayuki; Snowden, Pilar B; Nojima, Takuya et al. (2017) BCR and Endosomal TLR Signals Synergize to Increase AID Expression and Establish Central B Cell Tolerance. Cell Rep 18:1627-1635
Hwang, Joyce K; Wang, Chong; Du, Zhou et al. (2017) Sequence intrinsic somatic mutation mechanisms contribute to affinity maturation of VRC01-class HIV-1 broadly neutralizing antibodies. Proc Natl Acad Sci U S A 114:8614-8619
Kepler, Thomas B; Wiehe, Kevin (2017) Genetic and structural analyses of affinity maturation in the humoral response to HIV-1. Immunol Rev 275:129-144
Silva, Murillo; Nguyen, Thao H; Philbrook, Phaethon et al. (2017) Targeted Elimination of Immunodominant B Cells Drives the Germinal Center Reaction toward Subdominant Epitopes. Cell Rep 21:3672-3680

Showing the most recent 10 out of 14 publications