B cell antigen presentation plays a limited role in primary and secondary CD4 T cell responses (176.16)

Abstract

Abstract The activation and differentiation of effector CD4 T cells depends on interactions with MHCII-expressing antigen presenting cells (APCs). While several APC populations coordinate CD4 T cell function, several lines of evidence indicate that antigen presentation by B cells is a critical element to the cellular immune response. We have sought to determine the contribution of B cell antigen presentation to CD4 T cell priming and secondary responses. To address the hypothesis that B cells are sufficient APCs for CD4 T cell responses, we have designed a new tool in which individual subsets of APCs conditionally express MHCII in vivo. We successfully targeted a loxP-flanked stop sequence to the murine IA-β chain locus to utilize the Cre/lox system for conditional expression of MHCII. Conditional manipulation was achieved using CD19-Cre mice, restricting expression of MHCII to B cells. After priming, sub-optimal proliferation and activation of CD4 T cells was observed in mice expressing MHCII only by B cells. Further, limiting MHCII expression to B cells constrained secondary CD4 T cell responses in vivo. In a CD4 T cell-dependent model of autoimmunity, EAE, B cell expression of MHCII was not sufficient to support secondary autoreactive CD4 T cell responses targeting the CNS. These results demonstrate a novel capacity to conditionally express MHCII in vivo and highlight the limitations of B cell antigen presentation during the initiation and propagation of CD4 T cell function