CD19+ cells produce IFN-γ in mice infected withBorrelia burgdorferi

Abstract

We have recently shown that production of IFN‐γ and IL‐10, but not IL‐4 is specifically induced in the lymph nodes of C3H/HeJ (disease susceptible) and C57BL/6J (disease resistant) mice 1 week after infection with Borrelia burgdorferi spirochetes. The present study was conducted to determine the phenotypes of ex vivo lymph node cells obtained from infected mice of both strains at this time point. The percentages of CD3+, CD4+, CD8+, TCRα/β + and TCR γ/δ + cells decreased in both strains of mice compared to LN from naive mice. In contrast, there was a threefold increase in the proportion of CD19+ cells. In view of this expansion of the B cell proportion, we examined the ability of purified CD19+ cells and CD43+ cells to produce both IL‐10 and IFN‐γ when the cells were restimulated in vitro with B. burgdorferi freeze‐thawed spirochetes. As expected, CD43+ cells were able to produce both cytokines, but not IL‐4. Surprisingly, CD19+ (B) cells also were able to produce IFN‐γ in comparable amounts, in addition to IL‐10. Intracellular staining of CD19+ cells with anti‐IFN‐γ antibody confirmed this finding. We discuss this novel phenomenon in terms of its possible underlying mechanisms and its relevance, both in the context of the immunology of Lyme disease and that of other infectious diseases.

IL-4–producing B cells regulate T helper cell dichotomy in type 1- and type 2-controlled diseases

“…B cells that secreted higher amounts of IFN-γ and IL-12 were termed B effector 1 cells (Be1 cells), while B cells that produced more IL-4, IL-13, IL-10, and IL-2 were named Be2 cells. To date, these subsets of cytokine-producing B cells have been implicated in various mouse models of parasitic and bacterial infection (2,7,8,45,46), in models of ulcerative colitis (10) and autoimmunity (11,47), and in human infectious and autoimmune diseases (45,48,49). However, with the exception of IL-10 and, recently, type I IFNs (40), the functional role of B cell-derived cytokines in human leishmaniasis and schistosomiasis have until now not been investigated.…”

Role of interferon-γ in the evolution of murine bleomycin lung fibrosis

“…It has been shown that stimulation with IL-12 and IL-18 can induce IFN-␥ production by B cells in vivo and in vitro (34). IFN-␥ production by B lymphocytes has also been demonstrated in human tonsils (1) and in mice infected with Borrelia burgdorferi (13). IFN-␥ expression appears to be limited to immature B cells (1,12) and has autocrine effects on cell migration (12).…”

Regulation of IFN-γ Production by B Effector 1 Cells: Essential Roles for T-bet and the IFN-γ Receptor

“…Furthermore, naive B cells can be induced to differentiate into discrete B cell effector subsets that will produce differential arrays of cytokines upon restimulation, and these cytokine-producing effector B cells can modulate T cell responses (3). Cytokine-producing B cell effectors have been identified in the draining lymph nodes and spleens of autoimmune mice (4 -6) and mice infected with pathogens that induce strong type 1 or type 2 immunity (3,7,8). Importantly, cytokine-producing B cells play a critical protective role in several autoimmune disease models, including inflammatory bowel disease (4), experimental autoimmune encephalomyelitis (6), and collagen-induced arthritis (5).…”

“…Although IFN-␥-producing B cells have been identified in mice infected with pathogens such as Toxoplasma gondii and Borrelia burgdorferi (3,7), the molecular mechanisms that regulate IFN-␥ production by B cells are not known. It has been previously shown that B cells produce IFN-␥ in response to Ag (9) and to cytokines such as IL-12 and IL-18 (10,11).…”