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Member Information
John Monroe, PhD
Professor, Pathology and Laboratory Medicine
Chair, Immunology Graduate Program
Office Phone: 215-898-2873
Office Fax: 215-573-2014
Email: monroej@mail.med.upenn.edu
Website(s):
Education: PhD 1993, Duke University - Immunology
Keywords: immunology, signal transduction, lymphocyte development, B lymphocytes, tolerance
Research and/or Clinical Interests:
Study of B lymphocyte activation and tolerance and the mechanisms of signal transduction through the B lymphocyte antigen receptor.
Summary:
The laboratory studies development, activation, apoptosis and regulation of proliferation of B lymphocytes mediated by the B cell antigen receptor (BCR) complex and regulated by lineage-restricted transcription factors. Depending upon the activation state, the stage of development, or the strength of the signal generated, a signal generated through the BCR results in very different B lymphocyte responses. For example, at the pre-B cell stage, BCR signaling triggers allelic exclusion, expansion of pre-B cells and developmental progression. In contrast, BCR signal transduction leads to apoptosis of immature-stage B cells. This latter process is believed be the underlying mechanism regulating negative selection among immature B cells in the bone marrow. Finally, at the mature B cell stage, signaling leads to the growth and proliferation. We study the molecular processes regulating the coupling of BCR signals to specific cellular responses in order to define the processes in normal and disease prone mice that regulate positive and negative selection events during B cell development and an active immune response. Our current studies focus on the following specific questions.
Signal transduction and apoptosis . The biochemical regulation of negative selection and tolerance among immature-stage B cells. This is an active process requiring new RNA and protein synthesis whose role in normal B cell development is to facilitate the elimination of potentially autoimmune B cells. Currently, we are in the process of identifying the signaling pathways involved in determining whether engagement of the BCR leads to apoptosis or activation.
B and T cell development . We are studying early B cell development by studying the extrinsic and intrinsic regulation of commitment of multipotential precursor cells to cells committed to the B cell lineage. Specifically, the role of the lineage-restricted transcription factor Pax-5 is being studied in vivo and in vitro systems in order to ascertain its role in hematopoietic lineage determination and the mechanism by which these effects are regulated.
Leukemia and lymphoma . The role played by HIV in the direct stimulation of B lymphocyte proliferation is being studied. Clinical evidence supports the conclusion that HIV has direct proliferative effects on resting B cells. We are studying molecular regulation of these proliferative response and its relationship to the development of B cell lymphoma, common to HIV infected individuals.
Representative Publications:
Sater, R.A., Sandel, P.C., and Monroe , J.G. 1998. BCR-induced apoptosis in primary transitional murine B cells: Signaling requirements and modulation by T cell help. Int. Immunol. 10:1673-1682.
King, L., Norvell, A., and Monroe , J.G. 1999. Antigen receptor-induced signal transduction imbalances associated with the negative selection of immature B cells. J. Immunol.. 162:2655-2662.
Sandel, P.C. and Monroe , J.G. 1999. Negative selection of immature B cells by receptor editing or deletion is determined by site of antigen encounter. Immunity 10:289-299.
Chiang, M.Y. and Monroe , J.G. 1999. BSAP/Pax5A expression blocks survival and expansion of early myeloid cells implicating its involvement in maintaining commitment to the B lymphocyte lineage. Blood, in press.
Monroe , J.G. 1999. BCR signaling in immature-stage B cells: Integrating intrinsic and extrinsic signals. Current Topics in Microbiology and Immunology: in press.
