Helper B Cells Promote Cytotoxic T Cell Survival and Proliferation Independently of Antigen Presentation through CD27/CD70 Interactions

Abstract

CD8-expressing cytotoxic T cell (CTL) interactions with APCs and helper T cells determine their function and ability to survive. In this study, we describe a novel interaction independent of Ag presentation between activated CTLs and bystander CD19-expressing B lymphocytes. Ag-stimulated CTLs serially engage autologous B lymphocytes through CD27/CD70 contact that promotes their survival and proliferation. Moreover, these interactions induce the release of proinflammatory cytokines that follows two general patterns: 1) an epitope-dependent enhancement of cytokine release, and 2) a previously undiscovered coordinate release of cytokines independent of epitope exposure. The latter includes chemoattractants targeting activated T cells. As a result, activated T cells are attracted to B cells, which exert a “helper” role in lymphatic organs or in areas of inflammation. This observation provides a mechanistic explanation to previously reported experimental observations suggesting that B cells are required for T cell priming in vivo.

CD20+ B Cells: The Other Tumor-Infiltrating Lymphocytes

“…Conversely, Be-1 and Be-2 cells can promote the differentiation of Th1 and Th2 cells, respectively, such that polarized cytokine profiles of both B cells and Th cells are amplified and maintained (79,80). B cells also facilitate the formation of CD4 + T cell memory (81) and promote the survival and proliferation of activated CD8 + T cells through CD27-CD70 interactions (82). B cells also engage in negative regulatory relationships.…”

“…In a striking example of immunoregulation, B cells can promote the formation of TLSs by secreting lymphotoxin and chemokines, which attract and stimulate T cells, DCs, and other immune cells (7,82,84,85). Accordingly, elimination of B cells in RA or renal allografts results in the disintegration of TLSs with consequent diminution of T cell activity (13,16,29,30).…”

The immunologic constant of rejection

“…This association has never been observed in other varieties of immune-mediated tissue destruction. What these graft infiltrated and activated B cells are doing is unclear, but it is possible that they are powerful stimulators of T-cell responses through the production of CXCL chemokines that attract activated cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells [14]. This powerful combined immune reaction may set allograft rejection apart from other immune pathologies with the exception of some autoimmune diseases.…”

Antigen-Presenting Cell (APC) Subsets in Ovarian Cancer

“…Second, while CD20 is present on the surface of all mature B cells [33][34][35], and CD19 is predominantly expressed on B cells [36] [39,40]. B cells are capable of influencing T cell memory, survival, and proliferation [41,42], as well as presenting antigen to both CD4 + and CD8 + T cells [38,43] …”