CD40-Activated B Cells Can Efficiently Prime Antigen-Specific Naïve CD8⁺ T Cells to Generate Effector but Not Memory T cells

<div><h3>Background</h3><p>The identification of the signals that should be provided by antigen-presenting cells (APCs) to induce a CD8⁺ T cell response <em>in vivo</em> is essential to improve vaccination strategies using antigen-loaded APCs. Although dendritic cells have been extensively studied, the ability of other APC types, such as B cells, to induce a CD8⁺ T cell response have not been thoroughly evaluated.</p> <h3>Methodology/Principal Findings</h3><p>In this manuscript, we have characterized the ability of CD40-activated B cells, stimulated or not with Toll-like receptor (TLR) agonists (CpG or lipopolysaccharide) to induce the response of mouse naïve CD8⁺ T cells <em>in vivo</em>. Our results show that CD40-activated B cells can directly present antigen to naïve CD8⁺ T cells to induce the generation of potent effectors able to secrete cytokines, kill target cells and control a <em>Listeria monocytogenes</em> infection. However, CD40-activated B cell immunization did not lead to the proper formation of CD8⁺ memory T cells and further maturation of CD40-activated B cells with TLR agonists did not promote the development of CD8⁺ memory T cells. Our results also suggest that inefficient generation of CD8⁺ memory T cells with CD40-activated B cell immunization is a consequence of reduced Bcl-6 expression by effectors and enhanced contraction of the CD8⁺ T cell response.</p> <h3>Conclusions</h3><p>Understanding why CD40-activated B cell immunization is defective for the generation of memory T cells and gaining new insights about signals that should be provided by APCs are key steps before translating the use of CD40-B cell for therapeutic vaccination.</p>