IL21 is a cytokine that is most highly expressed by a specific subpopulation of CD4-positive T cells termed T follicular helper (TFH) cells. IL21 is normally produced by TFH in response to bacterial or viral infections or immunization with various vaccines. Normally, IL21 promotes the activation and differentiation of antigen-specific B cells to passage germinal centers to become memory B cells or long-lived plasma cells that secrete specific antibodies at high levels. How B cells contribute to the process of TFH maturation and function has been unclear. We found that mice lacking expression of the serine/threonine kinase LKB1/STK11 specifically in B cells developed splenomegaly that, unexpected, was due to increased members of mature T cells in greatly expanded follicular T cell zones. This was associated with a 30-fold expansion in the numbers of TFH and great increases in the number and sizes of germinal centers. LKB1-deficient B cells produced high levels of IL6, a cytokine that stimulates plasma cell differentiation as well as the development of TFH. The expanded TFH population secreted high levels of IL21 in an IL6-dependent manner. These results suggest that manipulation of LKB1 could be beneficial for the treatment of IL21-dependent diseases and for enhancing responses to vaccines. B-1 B cells are now recognized as innate-like B cells in that they can produce IgM and IgA specific for certain bacteria and viruses without immunization providing a natural shield against infections in children. Although they were identified in mice over 30 years ago, it was only recently that we showed they were comprised of two subsets that could be distinguished by levels of expression of the cell surface enzyme, ENPP1 and they subsets displayed unique functions. To develop a molecular basis for understanding these distinctions, we characterized the gene expression profiles of the subsets using next generation sequencing. These studies identified differential expression of genes involved in cellular movement and immune trafficking. We are now using a human specific ENPP1 antibody to try to identify human B-1a-like cells. We will be able to use the functional and gene expression distinctions e have identified to characterize human ENPP1 expressing cells. Characterizing the binding of different immunoglobulin classes to receptors for their Fc portions has greatly expanded our understandings of their functions in vivo. Our recent studies of the recently described IgM Fc receptor demonstrated that it is required for normal B cell differentiation and homeostasis, responses to antigenic challenge and prevention of autoimmunity. Since a number of different names had we been used to describe the protein and the gene encoding it, we contributed to the development of a consensus nomenclature that resulted in the use of FCRM for the gene and FCRM for the protein.
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