Projects

The goals of the laboratory are to understand the regulation of plasma cell differentiation, migration, survival and function. Plasma cells are terminally-differentiated B cells that secrete high-affinity antibodies constitutively, following immunization and exposure to a pathogen. The quality, magnitude and longevity of the antibody response are dependent upon the differentiation and survival of these cells, which involves many signaling factors and auxiliary cell types. We have used intravital two-photon imaging to study plasma cell differentiation and migration in the lymph node and have found that that these cells exhibit a highly linear migration that is independent of g_αi chemotaxis. This migration is unique among lymphocytes and enables these cells to travel long distances crossing heterogeneous microenvironments to reach niches critical for their survival. In some cases, plasma cells may undergo malignant transformation during differentiation leading to neoplasms in humans such as multiple myeloma. Despite their critical role in immune function and disease, many fundamental questions remain regarding the physiology of plasma cells in vivo. We are using two-photon intravital imaging in combination with modern cellular and immunological tools to visualize and better understand the physiology of these cells under normal and pathological conditions. The current topics in the laboratory are focused on:

1. Plasma cell differentiation. What factors regulate selection and differentiation of germinal center B cells to plasma cell?

2. What factors control plasma cell migration to the bone marrow and subsequent long-lived survival and retention?

3. What factors control myeloma cell retention and migration in the bone marrow, which enables tumor progression?