B Lymphocytes Regulate Dendritic Cell (Dc) Function in Vivo

Abstract

Increasing evidence indicates that dendritic cells (DCs) are the antigen-presenting cells of the primary immune response. However, several reports suggest that B lymphocytes could be required for optimal T cell sensitization. We compared the immune responses of wild-type and B cell-deficient (μMT) mice, induced by antigen emulsified in adjuvant or pulsed on splenic dendritic cells. Our data show that lymph node cells from both control and μMT animals were primed, but each released distinct cytokine profiles. Lymph node T cells from control animals secreted interferon (IFN)-γ, interleukin (IL)-2, and IL-4, whereas those from μMT mice produced IFN-γ and IL-2 but no IL-4. To test whether B cells may influence the T helper cell type 1 (Th1)/Th2 balance by affecting the function of DCs, we immunized mice by transferring antigen-pulsed DCs from wild-type or mutant mice. Injection of control DCs induced the secretion of IL-4, IFN-γ, and IL-2, whereas administration of DCs from μMT animals failed to sensitize cells to produce IL-4. Analysis of IL-12 production revealed that DCs from μMT mice produce higher levels of IL-12p70 than do DCs from wild-type animals. These data suggest that B lymphocytes regulate the capacity of DCs to promote IL-4 secretion, possibly by downregulating their secretion of IL-12, thereby favoring the induction of a nonpolarized immune response.

Essential role for virus-neutralizing antibodies in sterilizing immunity against Friend retrovirus infection

“…In addition to antibody production, B cells also have been shown to play important roles in the stimulation of T cell responses through mechanisms such as antigen presentation (28)(29)(30)(31)(32). Thus, the requirement for B cells in vaccine protection against FV that we previously observed could have been due to defective secondary T cell responses rather than the lack of virus-specific antibodies.…”

Therapeutic B cell depletion impairs adaptive and autoreactive CD4+T cell activation in mice

“…Studies demonstrating a role for B cells in CD4 ϩ T cell priming have also predominantly used mice given anti-IgM antibody since birth (30)(31)(32)(33) or mice with genetic defects in B cell development (34). In some studies, the absence of B cells can impair CD4 ϩ T cell priming (28,31,32,35,36), whereas in other studies, CD4 ϩ T cell priming was not affected (7,(37)(38)(39)(40). However, the absence of B cells during mouse development results in significant quantitative and qualitative abnormalities within the immune system, including a remarkable decrease in thymocyte numbers and diversity (41), significant defects within spleen DC and T cell compartments (7,42,43), an absence of Peyer's patch organogenesis and follicular DC networks (44,45), and an absence of marginal zone and metallophilic macrophages, with decreased chemokine expression (43,45).…”

“…Despite the benefits of this immunotherapy, the cellular and molecular basis for the protective effect mediated by B cell depletion is unknown (4). Understanding the mechanisms underlying the therapeutic benefit of B cell depletion is complicated by the fact that B cells not only produce autoantibodies (5) but also release inflammatory or immunomodulatory cytokines (6), regulate lymphoid tissue neogenesis and structure, provide costimulatory signals, alter dendritic cell (DC) function and homeostasis (7), can function as antigen-presenting cells, promote naïve CD4 ϩ T cell differentiation into Th1 or Th2 subsets, and may influence regulatory T cell numbers and function (8).…”

Immune Contexture, Immunoscore, and Malignant Cell Molecular Subgroups for Prognostic and Theranostic Classifications of Cancers

“…B cells were also shown to inhibit cytotoxic T-cell responses in several tumor models (DeNardo et al, 2010), or to directly favor tumor growth and metastasis through the production of lymphotoxin and activation of LT receptor-expressing castration-resistant prostate cancer cells (Ammirante, Luo, Grivennikov, Nedospasov, & Karin, 2010). However, some of these studies have to be interpreted with caution, as they were performed in μMT B-cell-deficient mice, known to display severe immune system abnormalities ( João, Ogle, Gay-Rabinstein, Platt, & Cascalho, 2004;Moulin et al, 2000). In addition, while some of these studies were based on total mouse B-cell depletion, several subpopulations of B cells have now been identified, including the immunomodulatory "Bregs" (Balkwill, Montfort, & Capasso, 2013;Rosser & Mauri, 2015).…”