No abstract

Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infections in infants and is characterized by pulmonary infiltration of B cells in fatal cases. We analyzed the B cell compartment in human newborns and identified a population of neonatal regulatory B lymphocytes (nBreg cells) that produced interleukin 10 (IL-10) in response to RSV infection. The polyreactive B cell receptor of nBreg cells interacted with RSV protein F and induced upregulation of chemokine receptor CX3CR1. CX3CR1 interacted with RSV glycoprotein G, leading to nBreg cell infection and IL-10 production that dampened T helper 1 (Th1) cytokine production. In the respiratory tract of neonates with severe RSV-induced acute bronchiolitis, RSV-infected nBreg cell frequencies correlated with increased viral load and decreased blood memory Th1 cell frequencies. Thus, the frequency of nBreg cells is predictive of the severity of acute bronchiolitis disease and nBreg cell activity may constitute an early-life host response that favors microbial pathogenesis.

IntroductionDendritic cells (DCs) are potent professional APCs that sensitize T cells to switch on appropriate immune responses to Ag danger signals. For this to occur, they take up Ags in peripheral tissues and transport them to lymphoid organs, where they interact with T cells to prime a specific response. 1 This property of DCs implies particular characteristics, including high expression of HLA class II molecules for efficient Ag presentation, high expression of CD80 and CD86 costimulatory molecules, and production of T-cell activating cytokines, such as IL-12, to trigger differentiation of T cells into efficient Th1 effector cells. 2 To acquire these characteristics, DC precursors differentiate into immature (iDC) and then to mature DCs (mDCs) 3 as a result of activation mediated by GM-CSF and IL-4 and by TLR-activating products such as lipopolysaccharides (LPS). However, the functional properties of DCs vary depending on the stage of maturation. Thus, mDCs stimulate T-cell immunity, whereas iDCs favor T-cell tolerance rather than immunity. 4 Furthermore, autoimmune diseases such as systemic lupus erythematosus (SLE) might result from break-in peripheral tolerance because of the activation of DCs. 5 If so, the control of the maturation and function of DCs should provide important tools to modulate aberrant autoimmune and inflammatory responses. 6,7 B cells were first recognized as immune cells committed to Ab production, ie, defined as effector cells of the humoral immune response. However, the authors of numerous studies have since discovered that B cells are regulators of immunity. 8 They have the ability to synthesize cytokines, 9 to act as APCs for T cells, 10 and to govern the architecture of secondary lymphoid organs by encouraging the development of DCs. 11 Moreover, murine models of autoimmune and inflammatory diseases have suggested that B cells also may regulate pathologic processes.After the release of one or several mediators and/or direct cell-to-cell contacts, B cells can modulate DC functions and consequently immune responses. Thus, in mice with lupus, autoreactive B cells contribute to the severity of the disorder once activated through their TLR9 but also exert a negative role on DC function if they secrete considerable amount of In the MT mouse model of arthritis, B cells are lacking and hence, DCs produce high quantities of proinflammatory IL-12p70 and do not secrete IL-4, compared with wild-type mice. This DC-mediated exacerbation of the inflammatory response is caused by the absence of IL-10 high -secreting B cells. 13 The results of these experiments suggest that B cells have the ability to regulate DC functions and thereby to control the induction of immune responses. However, much evidence indicates that B cells can also modulate the immune reactions by controlling T-cell responses. For example, in the TCR␣ Ϫ/Ϫ Ig Ϫ/Ϫ murine model of inflammatory bowel disease, 14 the development of spontaneous chronic colitis is downregulated by the transfer of B cells from TCR␣ Ϫ/Ϫ mice. B cells i...