Splenic antigen presenting cells and their role in shaping the immune response

Abstract

Antigen presenting cells (APCs) represent one of the most important cell types of the immune system. They are crucial for the initiation of protective adaptive immune response as well as for maintenance of tolerogenic conditions and tissue homeostasis. Therefore, how the function of APCs is regulated represents extremely important aspect in understanding the decisions made during immune response. The work presented here addressed the questions how single molecules, cellular composition of the spleen and particular anatomical location influence the character and outcome of immune response. The obtained results show that IFN-s and type I IFNs signaling are essential factors for proper antigen presentation and T cell activation by splenic conventional dendritic cells (DCs) in steady state. Absence of IFN-s leads to down-regulation of members of Hsp70 family in splenic DCs, which serve as molecular chaperones during antigen presentation via both MHC I and MHC II. Furthermore presented data show that absence of T and B cells has important implications on character and function of splenic DCs. Namely, DCs isolated from T and B cell deficient mice are impaired in presentation of soluble antigen. Finally particular anatomical location and high expression of CD1d on the surface of marginal zone (MZ) B cells enable them to be very efficient activators of NKT cells in vitro and in vivo. Interestingly, stimulation of NKT cells by MZ B cells lead to exclusive production of IL-4 in contrast to DCs. Taken together these work show how the antigen presentation by splenic DCs is regulated in homeostatic conditions. Importantly, it reveals the sensitivity of this process and may contribute to a deeper understanding of the initiation of the TH1 versus TH2 bias.