In experiments involving inhibitory drugs, T and B cells were pretreated at 37C before coincubation with their targets. target cells in the presence of inhibitors. Trogocytosis thus has different requirements in different cell types. Moreover, the capture of membrane antigen by B cells is identified as a novel signaling-independent event of B-cell biology. Introduction T lymphocytes and B lymphocytes are the 2 main cell types responsible for the adaptive immune response in vertebrates. Whereas B cells recognize native, unprocessed antigens IRAK inhibitor 3 using their B-cell receptor (BCR), T cells recognize antigenic peptides bound to major histocompatibility complex (MHC) molecules on the surface of antigen-presenting cells (APCs) using their T-cell receptor (TCR). Antigen recognition results in activation of the lymphocytes, the acquisition of their effector functions, and their cooperation with other cell types in the course of the adaptive immune response. Like many receptors on the cell surface, the antigen receptors on the surface of lymphocytes are taken up into the cell by endocytosis together with the antigens they bind.1,2 This is surprising because the antigens recognized by the TCR, the peptide-MHC complexes, are integral membrane proteins, which do not Rabbit Polyclonal to HDAC7A normally pass from one cell membrane to another. This observation, first reported for CD8+ cytotoxic T lymphocytes (CTLs),2 was confirmed by several other studies of the 2 2 major classes of T cell: CD8+ (CTL) and CD4+ (helper) T cells.3 Likewise, in an elegant system developed by Batista et al, B cells have also been reported to acquire antigens that are membrane-bound and to be able to introduce them, like soluble antigens, in the presentation pathway.4 Our group has demonstrated that peptides bound to MHC complexes translocate from the APC to the T cell in membrane fragments that contain both lipids and many other membrane-bound proteins.5 We coined the term trogocytosis to describe this process of unidirectional transfer of plasma membrane material from target cells to effector cells of the immune system.6 Initially, using well-characterized murine models of antigen-specific lymphocytes, we made this observation in CD8+ CTLs but, later, we showed that CD4+ T cells and B cells also perform trogocytosis (ie, they acquire membrane-anchored antigen in fragments of membrane).7,8 Trogocytosis has since also been reported for most other hematopoietic cells including natural killer (NK) cells (see Roda-Navarro and Reyburn9 for a review), dendritic cells,10 monocytes,11,12 and neutrophils,13 indicating that antigen recognition by antigen receptors is not the only molecular trigger for trogocytosis. Worthy of note, activated but not resting CD4+ and CD8+ T cells were shown to acquire membrane patches from target cells in the absence of antigen and independently of the TCR.14C16 Trogocytosis is now a well-recognized feature of T- and B-cell biology, and numerous hypotheses propose that the process is involved in the control of immune responses or in the spreading of pathogens.3,6,17,18 The lack of information about the molecular players involved in trogocytosis is a major obstacle to understanding the mechanism and the roles that the process may play in different cell types. In comparison with T cells5,8,15,19C21 and with NK cells (see Roda-Navarro and Reyburn9 for a review), much less is known on the parameters governing B-cell trogocytosis. The acquisition of antigen by B cells is a central process of adaptive immunity that has been known for decades. Upon antigen recognition, the B cell internalizes the antigen, processes IRAK inhibitor 3 it into protein fragments, and presents these peptides bound to MHC class II molecules on its own surface. This peptide-MHC complex IRAK inhibitor 3 is then recognized by CD4+ helper T cells, which stimulate the B cell to secrete antibodies (Abs).