Browsing by Author "Kelsoe, Garnett"
Now showing items 1-20 of 23
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3Conserved cryptic recombination signals in V kappa gene segments are cleaved in small pre-B cells
(BMC IMMUNOLOGY, 2009-06-25) -
A functional analysis of the spacer of V(D)J recombination signal sequences.
(PLoS Biol, 2003-10)During lymphocyte development, V(D)J recombination assembles antigen receptor genes from component V, D, and J gene segments. These gene segments are flanked by a recombination signal sequence (RSS), which serves as the ... -
Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus.
(Nature, 2013-04-25)Current human immunodeficiency virus-1 (HIV-1) vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in approximately 20% of HIV-1-infected individuals, and details ... -
Germinal center entry not selection of B cells is controlled by peptide-MHCII complex density.
(Nature communications, 2018-03-02)B cells expressing high affinity antigen receptors are advantaged in germinal centers (GC), perhaps by increased acquisition of antigen for presentation to follicular helper T cells and improved T-cell help. In this model ... -
H3N2 influenza infection elicits more cross-reactive and less clonally expanded anti-hemagglutinin antibodies than influenza vaccination.
(PloS one, 2011-01)During the recent H1N1 influenza pandemic, excess morbidity and mortality was seen in young but not older adults suggesting that prior infection with influenza strains may have protected older subjects. In contrast, a history ... -
HIV-1 envelope gp41 broadly neutralizing antibodies: hurdles for vaccine development.
(PLoS Pathog, 2014-05) -
Identification and utilization of arbitrary correlations in models of recombination signal sequences.
(Genome Biol, 2002)BACKGROUND: A significant challenge in bioinformatics is to develop methods for detecting and modeling patterns in variable DNA sequence sites, such as protein-binding sites in regulatory DNA. Current approaches sometimes ... -
Identification of autoantigens recognized by the 2F5 and 4E10 broadly neutralizing HIV-1 antibodies.
(J Exp Med, 2013-02-11)Many human monoclonal antibodies that neutralize multiple clades of HIV-1 are polyreactive and bind avidly to mammalian autoantigens. Indeed, the generation of neutralizing antibodies to the 2F5 and 4E10 epitopes of HIV-1 ... -
IGHV1-69 B cell chronic lymphocytic leukemia antibodies cross-react with HIV-1 and hepatitis C virus antigens as well as intestinal commensal bacteria.
(PLoS One, 2014)B-cell chronic lymphocytic leukemia (B-CLL) patients expressing unmutated immunoglobulin heavy variable regions (IGHVs) use the IGHV1-69 B cell receptor (BCR) in 25% of cases. Since HIV-1 envelope gp41 antibodies also frequently ... -
Immune checkpoint modulation enhances HIV-1 antibody induction.
(Nature communications, 2020-02-19)Eliciting protective titers of HIV-1 broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development, but current vaccine strategies have yet to induce bnAbs in humans. Many bnAbs isolated from HIV-1-infected ... -
Inflammation and the reciprocal production of granulocytes and lymphocytes in bone marrow.
(J Exp Med, 2005-06-06)The coordinated production of leukocytes in bone marrow is crucial for innate and adaptive immunity. Inflammation alters normal leukocyte production by promoting granulopoiesis over lymphopoiesis, a response that supports ... -
Inflammation controls B lymphopoiesis by regulating chemokine CXCL12 expression.
(J Exp Med, 2004-01-05)Inflammation removes developing and mature lymphocytes from the bone marrow (BM) and induces the appearance of developing B cells in the spleen. BM granulocyte numbers increase after lymphocyte reductions to support a reactive ... -
Inflammation triggers emergency granulopoiesis through a density-dependent feedback mechanism.
(PLoS One, 2011)Normally, neutrophil pools are maintained by homeostatic mechanisms that require the transcription factor C/EBPα. Inflammation, however, induces neutrophilia through a distinct pathway of "emergency" granulopoiesis that ... -
Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated.
(J Exp Med, 2011-10-24)The initial antibody response to HIV-1 is targeted to envelope (Env) gp41, and is nonneutralizing and ineffective in controlling viremia. To understand the origins and characteristics of gp41-binding antibodies produced ... -
Initiation of HIV neutralizing B cell lineages with sequential envelope immunizations.
(Nature communications, 2017-11-23)A strategy for HIV-1 vaccine development is to define envelope (Env) evolution of broadly neutralizing antibodies (bnAbs) in infection and to recreate those events by vaccination. Here, we report host tolerance mechanisms ... -
Isolation of HIV-1-neutralizing mucosal monoclonal antibodies from human colostrum.
(PLoS One, 2012)BACKGROUND: Generation of potent anti-HIV antibody responses in mucosal compartments is a potential requirement of a transmission-blocking HIV vaccine. HIV-specific, functional antibody responses are present in breast milk, ... -
Multiple, conserved cryptic recombination signals in VH gene segments: detection of cleavage products only in pro B cells.
(J Exp Med, 2007-12-24)Receptor editing is believed to play the major role in purging newly formed B cell compartments of autoreactivity by the induction of secondary V(D)J rearrangements. In the process of immunoglobulin heavy (H) chain editing, ... -
Polyclonal B cell differentiation and loss of gastrointestinal tract germinal centers in the earliest stages of HIV-1 infection.
(PLoS Med, 2009-07-07)BACKGROUND: The antibody response to HIV-1 does not appear in the plasma until approximately 2-5 weeks after transmission, and neutralizing antibodies to autologous HIV-1 generally do not become detectable until 12 weeks ... -
Prospective estimation of recombination signal efficiency and identification of functional cryptic signals in the genome by statistical modeling.
(J Exp Med, 2003-01-20)The recombination signals (RS) that guide V(D)J recombination are phylogenetically conserved but retain a surprising degree of sequence variability, especially in the nonamer and spacer. To characterize RS variability, we ... -
Recapitulation of HIV-1 Env-antibody coevolution in macaques leading to neutralization breadth.
(Science (New York, N.Y.), 2020-11-19)Neutralizing antibodies elicited by HIV-1 coevolve with viral envelope proteins (Env) in distinctive patterns, in some cases acquiring substantial breadth. We report that primary HIV-1 envelope proteins-when expressed by ...
