Cancer Institute A national cancer institute
designated cancer center

Role of B Cells in Tumor Biology

The laboratory of Leonore Herzenberg focuses on gene regulation in the immune system, development and function of B cell subpopulations, and applications of fluorescence activated cell sorting. Dr. Herzenberg was the first to identify Ly-1B (CD5) expressing B cells, which follow different rules of differentiation than conventional B cells, have different variable gene repertoires and provide a model for chronic lymphocytic leukemia and for autoimmune diseases.

Recently, the lab devised a method to study gene regulation at the individual cell level using the FACS and a fluorogenic substrate for E. coli lac-Z-encoded beta-galactosidase which greatly facilitates cell lineage studies.

CD72 as a Negative Regulator of B Cell Activation

The laboratory of Jane Parnes is studying how the B cell surface protein CD72 regulates both proliferation and apoptosis of B cells. The group generated CD72-deficient mice and found that the B cells in these mice are hyperproliferative to signals through the B cell receptor (BCR), supporting the concept of CD72 as a negative regulator of B cell activation.

To understand this regulatory role, the lab has been studying how CD72 modulates signaling in response to antigen stimulation. They have found that CD72 down-regulates the major signal transduction pathways downstream of the BCR, including NF-AT , NF -?B, ERK, JNK, p38-MAPK, and PI3K/AKT in mature B cells. They have additionally found that CD72-deficiency results in increased apoptosis of B cells following antigen stimulation.

The lab is interested in further exploring the mechanisms by which CD72 regulates both cell-cycle progression and apoptosis in mature B cells. Recently the group has found that lack of CD72 leads to a partial abrogation of B cell tolerance in a model system of anergic B cells using double-transgenic mice expressing a HEL-specific BCR on all B cells and soluble HEL in the serum.

These mice also develop spontaneous autoantibodies and glomerulonephritis as they age. Studies are planned to examine whether these mice might reject tumors more readily.

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