Philadelphia University + Thomas Jefferson University

Manser, Timothy

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Timothy L. Manser, PhD

Contact Dr. Manser

233 South 10th Street
302 BLSB
Philadelphia, PA 19107

(215) 503-4672
(215) 923-4153 fax

Research and Clinical 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 and the control of B cell autoreactivity.  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 microenvironmental locales (particularly the germinal center (GC)) in which these changes take place. We are predominantly interested in the fate of B cells with autoreactive antigen receptors (either pre-existing or acquired via V region hypermutation) during memory B cell development. Additional projects concern the role of Fc receptors, the BAFF (BLyS) pathway, follicular dendritic cells and follicular helper T cells in the regulation of the B cell response. We have also recently established hematopoietically humanized mouse technology. We will be using this approach to study human autoimmune and infectious disease, as well as cancer immunotherapy in collaboration with other members of the Department and the Medical College.

Publications

Most Recent Peer-Reviewed Publications

  1. 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
  2. Cutting edge: Macrophages are required for localization of antigen-activated b cells to the follicular perimeter and the subsequent germinal center response
  3. A germline-competent embryonic stem cell line from NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice
  4. Direct reduction of antigen receptor expression in polyclonal B cell populations developing in vivo results in light chain receptor editing
  5. Characteristics of Borrelia hermsii infection in human hematopoietic stem cell-engrafted mice mirror those of human relapsing fever
  6. Immunologic research at Thomas Jefferson University: A recent history
  7. Human immune system mice: Current potential and limitations for translational research on human antibody responses
  8. Cellular competition independent of BAFF/B lymphocyte stimulator results in low frequency of an autoreactive clonotype in mature polyclonal B cell compartments
  9. Expression of cellular FLIP by B cells is required for their participation in an immune response
  10. Germinal center reutilization by newly activated B cells
  11. The lupus susceptibility locus Sle1 breaches peripheral B cell tolerance at the antibody-forming cell and germinal center checkpoints
  12. Initial Clonal Expansion of Germinal Center B Cells Takes Place at the Perimeter of Follicles
  13. Influence of B cell antigen receptor expression level on pathways of B cell tolerance induction
  14. A role for cFLIP in B cell proliferation and stress MAPK regulation
  15. Specialization and Complementation of Humoral Immune Responses to Infection: Preface
  16. Influence of fas on the regulation of the response of an anti-nuclear antigen B cell clonotype to foreign antigen
  17. 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
  18. Expression of the autoimmune Fcgr2b NZW allele fails to be upregulated in germinal center B cells and is associated with increased IgG production
  19. 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
  20. Autoantigen-B cell antigen receptor interactions that regulate expression of B cell antigen receptor loci