B lymphocytes acquire and present intracellular antigens that have relocated to the surface of apoptotic target cells

Abstract

The induction of an effective immune response requires the activation of CD4+ T lymphocytes by APCs. While DCs have been shown to be pivotal in this process, it is now apparent that optimal CD4+ T-cell activation also requires B-lymphocyte APC function. Along with the acquisition of soluble antigens, it is known that B cells also acquire membrane-tethered antigens. Recent reports have described the relocation of intracellular antigens to the cell surface following immunogenic apoptosis. This study was designed to determine whether B cells can acquire and present such antigens to CD4+ T cells. By targeting the model antigen tetanus toxin C fragment to various cellular locations, we show that antigen-specific B cells acquire intracellular antigens that have relocated to the surface of cells undergoing immunogenic apoptosis. Crucially, we also demonstrate that antigen-specific B cells acquiring relocated antigen from apoptotic targets are capable of efficiently inducing CD4+ T-cell activation. We propose that the acquisition and presentation of intracellular antigens that have relocated to the cell surface during immunogenic apoptosis represents a novel means by which antigen-specific B cells contribute to the generation of immunity. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.