Immunology Graduate Group

.Stephan A. Grupp, M.D., Ph.D.
Division of Pediatric Oncology
Children's Hospital of Philadelphia

Office Phone:  (215) 590-5475
Email:  grupp@email.chop.edu

Education:

B.S., Biology, University of Cincinnati
Ph.D., Immunology, University of Cincinnati College of Medicine
M.D., University of Cincinnati College of Medicine


Research Interests

Role of the B cell receptor complex in B cell signaling and lymphoid development

Research Summary

Our major research interest is in the area of B cell development from committed lymphoid progenitor to mature B cell.  The B cell receptor complex lends antigen specificity to most of the functions of the mature B cell. These include antigen binding for subsequent presentation to helper T cells, as well as the process of antigen-mediated B cell activation. In pre-B cells, immunoglobulin (m) heavy chain is part of a pre-B cell receptor complex, which also includes the Iga/b heterodimer and surrogate light chains. Current studies ongoing in the lab include the role of m heavy chain in early B cell development, specifically the transition through the pre-B cell stage, apoptotic cell death, allelic exclusion and activation of light chain rearrangement. These studies are being carried out in vivo using IgM transgenic mice and in vitro using transfected pro- and pre-B cell lines. Recent studies have helped to confirm the importance of Iga/b in B cell development as well as elucidate the relative contributions of signaling via Iga/b and surrogate light chains in both development and allelic exclusion.  

Expressions of transgenic human mD protein blocks development of B cells in FVB mice. Total B cell number in the spleen is significantly decreased in mD transgenic mice compared to non transgenic littermates and m transgenic mice. Most B cells in mD transgenics are transgenic m negative, while almost all B cells in m transgenic mice express the transgenic protein.
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The block in B cell development is at the pre-B cell level, as shown by the near absence of pre-B cells in the bone marrow of mD transgenic mice. The cells shown in this cytometric analysis are all B220+, and then analyzed for expression of CD43 and IgM. These pre-B cells are B220+CD43- IgM-.





Dr. Stephan A. Grupp
The block in B cell development is at the pre-B cell level, as shown by the near absence of pre-B cells in the bone marrow of mD transgenic mice. The cells shown in this cytometric analysis are all B220+, and then analyzed for expression of CD43 and IgM. These pre-B cells are B220+CD43- IgM-.

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