Lymphopenia in a Dominant Activating Rac2 Mutation Mouse Model

Lana Purdy, Melanie Rodriguez, Denise Montell

Rac is a Rho GTPase that functions as a molecular switch. Specifically, Rac2 regulates actin cytoskeleton rearrangement, membrane ruffling, and phagocytosis. Mutations in Rac2 can lead to human disease. The dominant activating mutation, Rac2E62K, results in a hyperactive form of Rac. Patients with this mutation suffer from immunodeficiency, recurrent pulmonary infections, as well as B and T cell lymphopenia. My project is focused on understanding the cause of the B cell lymphopenia in patients using the Rac2E62K mouse model. While this mutation leads to a loss of circulating B cells, our lab found that Rac2E62K mice have an accumulation of B cells in the spleen compared to wild-type mice. We hypothesize that the Rac2E62K mutation may disrupt B cell migration, differentiation, or both thus resulting in the B cell lymphopenia. To investigate this phenomenon, we did immunofluorescence staining to spatially map B cell distribution within the spleens of wild-type and Rac2E62K mice. As well as flow cytometry to quantitatively assess the different B cell populations residing within the mice spleens. Based on previous literature and our preliminary work we expect to see more marginal zone and follicular B cells as well as an increased number of mature and activated B cells compared to the wild-type control, suggesting that Rac2E62K disrupts B cell differentiation. From this data, we hope to further understand the cause of the B cell lymphopenia in patients and mice and ultimately, elucidate the role of hyperactive Rac in B cell development and migration.