Timothy L. Manser, PhD
Professor/Chair, Microbiology and Immunology

Contact Dr. Manser

1020 Locust Street
Room 471
Philadelphia, PA 19107

(215) 503-4672

Education
BA, University of California, San Diego, Biology, 1977
PhD, University of Utah, Biology, 1982

University Appointment
Professor/Chair
Microbiology and Immunology
Thomas Jefferson University

Research and Clinical Interests
Manser Laboratory Research Interests

Our laboratory’s interests center on the antigen-dependent stages of B cell differentiation in the mouse, leading to the generation of B cell memory. We are investigating the mechanisms responsible for antigen-driven changes in the structure and function of the antibody repertoire during memory development, as well as the micro environmental locales (particularly the germinal center (GC)) in which these changes take place. We are particularly interested in the fate of B cells with auto reactive antigen receptors, (either pre-existing or acquired via V region hyper mutation) during memory B cell development. Additional projects concern the role of Fc receptors, the BAFF (BLys) pathway, follicular dendritic cells and T cells in the regulation of the B cell response.

In the past, we have largely restricted our studies to immune responses to haptens in mouse models. Going forward, we would like to apply the lessons learned from these analyses to a better understanding of the factors that regulate antibody responses to neoplasia and infection in humans. As such, we are currently developing the technology necessary to generate mice that are “hematopoietically humanized”. In addition, we are planning future studies of the immune response of mice to viruses and bacteria. Participation in the Jefferson Vaccine Center initiative would be of great benefit to these ongoing and future studies. Reciprocally, our 25 years of experience in the analysis of B cell development and immune responses should be of substantial value to all Center Members for their studies.

Publications

1. A germline-competent embryonic stem cell line from NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice
2. Direct reduction of antigen receptor expression in polyclonal B cell populations developing in vivo results in light chain receptor editing
3. Characteristics of Borrelia hermsii infection in human hematopoietic stem cell-engrafted mice mirror those of human relapsing fever
4. Immunologic research at Thomas Jefferson University: A recent history
5. Human immune system mi Current potential and limitations for translational research on human antibody responses
6. Cellular competition independent of BAFF/B lymphocyte stimulator results in low frequency of an autoreactive clonotype in mature polyclonal B cell compartments
7. Expression of cellular FLIP by B cells is required for their participation in an immune response
8. Germinal center reutilization by newly activated B cells
9. The lupus susceptibility locus Sle1 breaches peripheral B cell tolerance at the antibody-forming cell and germinal center checkpoints
10. Initial Clonal Expansion of Germinal Center B Cells Takes Place at the Perimeter of Follicles
11. Influence of B cell antigen receptor expression level on pathways of B cell tolerance induction
12. A role for cFLIP in B cell proliferation and stress MAPK regulation
13. Specialization and Complementation of Humoral Immune Responses to Infection: Preface
14. Influence of fas on the regulation of the response of an anti-nuclear antigen B cell clonotype to foreign antigen
15. 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
16. Expression of the autoimmune Fcgr2b NZW allele fails to be upregulated in germinal center B cells and is associated with increased IgG production
17. Quantitatively reduced participation of anti-nuclear antigen B cells that down-regulate B cell receptor during primary development in the germinal center/memory B cell response to foreign antigen
18. Autoantigen-B cell antigen receptor interactions that regulate expression of B cell antigen receptor loci
19. FcγRIIB regulates autoreactive primary antibody-forming cell, but not germinal center B cell, activity
20. The Fas-associated death domain protein is required in apoptosis and TLR-induced proliferative responses in B cells

(This list reflects the most recent 20 publications)