Our research focuses on the function of B lymphocytes and qualitative aspects of immunological memory. We study the role of specific pathways affecting B cell development or function to understand processes that regulate B cell selection and differentiation. In several projects, we define antibody responses at the clonal level by single-cell sorting memory B cells for sequence analysis of antibody V(D)J transcripts and for isolation of antigen-specific monoclonal antibodies. We also apply next generation sequencing to analyze expressed immune repertoires and to trace specific antibody lineages to understand their fate and levels of affinity maturation. Because V(D)J gene assignment is a critical first step of lineage tracing, and there is considerable genetic variation in germline V genes/alleles between subjects, we developed a computational tool that allows the generation of individualized germline V gene databases, IgDiscover. This is a major technical advance that will enable the use of individualized germline databases to become a standard element of high quality immunological studies in both humans and experimental animals. By applying these methods we obtain new and highly detailed information about the establishment of long-lived immunity.
Particulate Array of Well-Ordered HIV Clade C Env Trimers Elicits Neutralizing Antibodies that Display a Unique V2 Cap Approach.
Immunity 2017 05;46(5):804-817.e7
Production of individualized V gene databases reveals high levels of immunoglobulin genetic diversity.
Nat Commun 2016 12;7():13642
Diverse antibody genetic and recognition properties revealed following HIV-1 envelope glycoprotein immunization.
J. Immunol. 2015 Jun;194(12):5903-14
B-1a transitional cells are phenotypically distinct and are lacking in mice deficient in IκBNS.
Proc. Natl. Acad. Sci. U.S.A. 2014 Sep;111(39):E4119-26
Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus escape variants.
J. Exp. Med. 2014 Nov;211(12):2361-72
HIV-1 receptor binding site-directed antibodies using a VH1-2 gene segment orthologue are activated by Env trimer immunization.
PLoS Pathog. 2014 Aug;10(8):e1004337
Single-cell and deep sequencing of IgG-switched macaque B cells reveal a diverse Ig repertoire following immunization.
J. Immunol. 2014 Apr;192(8):3637-44
Vaccine-elicited primate antibodies use a distinct approach to the HIV-1 primary receptor binding site informing vaccine redesign.
Proc. Natl. Acad. Sci. U.S.A. 2014 Feb;111(7):E738-47
A forward genetic screen reveals roles for Nfkbid, Zeb1, and Ruvbl2 in humoral immunity.
Proc. Natl. Acad. Sci. U.S.A. 2012 Jul;109(31):12286-93
High-resolution definition of vaccine-elicited B cell responses against the HIV primary receptor binding site.
Sci Transl Med 2012 Jul;4(142):142ra96
Soluble HIV-1 Env trimers in adjuvant elicit potent and diverse functional B cell responses in primates.
J. Exp. Med. 2010 Aug;207(9):2003-17
The challenges of eliciting neutralizing antibodies to HIV-1 and to influenza virus.
Nat. Rev. Microbiol. 2008 Feb;6(2):143-55