DESCRIPTION (provided by applicant): The essential micronutrient selenium (Se) is known to play a significant role in immune homeostasis and immune responses. Thus far, the majority of studies have focused on the effect of Se on either T cells or macrophages. In addition to these cells, B cells are well known for their involvement in immune homeostasis, yet the role of Se and selenoproteins in B cells has largely been understudied. There are evidence that Se may influence humoral responses in humans and animals. A few recent studies have noted the potential role of selenoproteins in B cell calcium signaling and protein folding. However, no studies to date have addressed the role of Se in B-cell receptor (BCR) signaling and its downstream effects such as B cell differentiation, proliferation, and immunoglobulin secretion. Redox status of B cells influences the B cell functions and differentiation. Given the central role of selenoproteins in regulating the redox status of cells, we hypothesized that selenoproteins influence B cell development and functions by regulating the redox status of cells. Preliminary studies indicated that BCR endocytosis and antigen trafficking to MHC class II compartments are significantly impaired in Se-deficient B cells. Defects in BCR endocytosis and antigen processing in Se-deficient B cells were associated with the higher levels of cellular ROS. Interestingly, BCR endocytosis and antigen degradation were accelerated in B cells isolated from Se-supplemented mice, suggesting that B cells functions could be enhanced by dietary Se-supplementation. The proposed study will be the first to establish the role of selenoproteins in B cell functions and development with the following specific aims: Specific Aim 1: Establish the role of selenoproteins in B cell antigen processing and presentation. To determine the contributions of selenoproteins to antigen processing and presentation, BCR endocytosis & signaling, antigen trafficking, degradation, and presentation will be measured in Se-deficient, Se-adequate and Se-supplemented B cells. Specific Aim 2: Examine the role of selenoproteins in B cell differentiation and development. Since we observed a significant reduction the frequency and number of B cells in the spleen of TrspB mice, B cell developmental stages in bone marrow and B cell subsets in peripheral tissues in TrspB mice will be compared with that of wild-type (WT) littermate controls. Specific Aim 3: Investigate the effect of Se in B cell-mediated immune responses. Immunoglobulin synthesis and secretion will be measured by in vitro assays using TrspB B cells. In addition, disease progression in models of acute tularemia and chronic bordetellosis, will be monitored in TrspB mice. The proposed studies will have a major impact on the field by addressing three critical questions: 1) What is the contribution of selenoproteins to the functions and development of B cells? 2) How do selenoproteins influence the memory res...