Manser Research

Contact

Name: Tim Manser, PhD
Position: Professor

233 South 10 Street
Suite 708
Philadelphia, PA 19107

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Highlighted Publications

Alabyev, B., Z. S. M. Rahman and T. ManserQuantitatively Reduced Participation of Anti-nuclear Antigen B Cells that Down Regulate BCR During Primary Development in the Germinal Center/memory B Cell Response to Foreign Antigen” (2007) J. Immunol. 178: 5623-5634.

This manuscript provided the first evidence for the action of a peripheral B cell tolerance “checkpoint” operating during the germinal center reaction.  Perturbation of this checkpoint may promote the development of systemic autoimmune diseases.

Coffey, F., B. Alabyev and T. ManserInitial clonal expansion of germinal center B cells takes place at the perimeter of follicles” (2009) Immunity 30: 599-609.

This paper showed for the first time that B cells undergoing a T cell dependent response proliferate and begin differentiation to germinal center B cells in a novel lymphoid microenvironment.  This defined a new stage of antigen-driven B cell development.

Vuyyuru, R., H. Liu, T. Manser and K. Alugupalli “The characteristics of Borrelia hermsii infection in human hematopoietic stem cell-engrafted mice mirror those of human relapsing fever” (2011) Proc. Natl. Acad. Sci. USA 108: 20707-20712.

This paper was the first to demonstrate that hematopoietically humanized mice could mount protective immune responses against bacterial infections.  Thus, these mice can be used as models for the development of anti-bacterial vaccines and therapeutics.

Walker, J., T. Manser and K. Alugupalli, “Humoral immunity in mice transplanted with hematopoietic stem cells derived from human umbilical cord blood recapitulates that of human infants” (2017) Stem Cells and Development, in press.

This paper highlighted the limitations of humanized mouse technology at present by showing that these mice do not respond to purified bacterial capsular polysaccharides.  This is also the case for human infants, suggesting that the immune systems of humanized mice recapitulate that of young children.

Recent Publications

Strongyloides stercoralis and htlv-1 coinfection in cd34+ cord blood stem cell humanized mice: alteration of cytokine responses and enhancement of larval growth

Maturation of the Humoral Immune Response: A Neo-Darwinian Process?

Humoral Immunity in Mice Transplanted with Hematopoietic Stem Cells Derived from Human Umbilical Cord Blood Recapitulates That of Human Infants

Human B-1 and B-2 B cells develop from Lin-CD34+CD38lo stem cells

YY1 is required for germinal center B cell development

Establishment and Characterization of Orthotopic Mouse Models for Human Uveal Melanoma Hepatic Colonization

Testing the role of the fcγγriib immunoreceptor tyrosine-based inhibitory motif in regulation of the b cell immune response

Evaluation of the efficiency of human immune system reconstitution in NSG mice and NSG mice containing a human HLA.A2 transgene using hematopoietic stem cells purified from different sources

Cutting edge: Macrophages are required for localization of antigen-activated b cells to the follicular perimeter and the subsequent germinal center response

A germline-competent embryonic stem cell line from NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice

Direct reduction of antigen receptor expression in polyclonal B cell populations developing in vivo results in light chain receptor editing

Characteristics of Borrelia hermsii infection in human hematopoietic stem cell-engrafted mice mirror those of human relapsing fever

Human immune system mice: Current potential and limitations for translational research on human antibody responses

Immunologic research at Thomas Jefferson University: A recent history

Cellular competition independent of BAFF/B lymphocyte stimulator results in low frequency of an autoreactive clonotype in mature polyclonal B cell compartments

Expression of cellular FLIP by B cells is required for their participation in an immune response

Germinal center reutilization by newly activated B cells

The lupus susceptibility locus Sle1 breaches peripheral B cell tolerance at the antibody-forming cell and germinal center checkpoints

Initial Clonal Expansion of Germinal Center B Cells Takes Place at the Perimeter of Follicles

A role for cFLIP in B cell proliferation and stress MAPK regulation

Influence of B cell antigen receptor expression level on pathways of B cell tolerance induction

Specialization and Complementation of Humoral Immune Responses to Infection: Preface

Influence of fas on the regulation of the response of an anti-nuclear antigen B cell clonotype to foreign antigen

Primary development and participation in a foreign antigen-driven immune response of a chromatin-reactive B cell clonotype are not influenced by TLR9 or other MyD88-dependent TLRs

Expression of the autoimmune Fcgr2b NZW allele fails to be upregulated in germinal center B cells and is associated with increased IgG production

Recent Publications

Humoral Immunity in Mice Transplanted with Hematopoietic Stem Cells Derived from Human Umbilical Cord Blood Recapitulates That of Human Infants

Human B-1 and B-2 B cells develop from Lin-CD34+CD38lo stem cells

YY1 is required for germinal center B cell development

Establishment and Characterization of Orthotopic Mouse Models for Human Uveal Melanoma Hepatic Colonization

Evaluation of the efficiency of human immune system reconstitution in NSG mice and NSG mice containing a human HLA.A2 transgene using hematopoietic stem cells purified from different sources

Cutting edge: Macrophages are required for localization of antigen-activated b cells to the follicular perimeter and the subsequent germinal center response

A germline-competent embryonic stem cell line from NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice

Direct reduction of antigen receptor expression in polyclonal B cell populations developing in vivo results in light chain receptor editing

Characteristics of Borrelia hermsii infection in human hematopoietic stem cell-engrafted mice mirror those of human relapsing fever

Immunologic research at Thomas Jefferson University: A recent history

Human immune system mice: Current potential and limitations for translational research on human antibody responses

Cellular competition independent of BAFF/B lymphocyte stimulator results in low frequency of an autoreactive clonotype in mature polyclonal B cell compartments

Expression of cellular FLIP by B cells is required for their participation in an immune response

Germinal center reutilization by newly activated B cells

The lupus susceptibility locus Sle1 breaches peripheral B cell tolerance at the antibody-forming cell and germinal center checkpoints

Initial Clonal Expansion of Germinal Center B Cells Takes Place at the Perimeter of Follicles

Influence of B cell antigen receptor expression level on pathways of B cell tolerance induction

A role for cFLIP in B cell proliferation and stress MAPK regulation

Specialization and Complementation of Humoral Immune Responses to Infection: Preface

Influence of fas on the regulation of the response of an anti-nuclear antigen B cell clonotype to foreign antigen