B Lymphocytes Are Required during the Early Priming of CD4+ T Cells for Clearance of Pneumocystis Infection in Mice

Abstract

B cells play a critical role in the clearance of Pneumocystis (PC). In addition to production of PC-specific antibody, B cells are required during the priming phase for CD4+ T cells to expand normally and generate memory. Clearance of PC was found to be dependent on antigen specific B cells and on the ability of B cells to secrete PC-specific antibody, as mice with B cells defective in these functions or with a restricted B cell receptor were unable to control PC infection. Because PC-specific antiserum was only able to partially protect B cell deficient mice from infection, we hypothesized that optimal T cell priming requires fully functional B cells. Using adoptive transfer and B cell depletion strategies, we determined that optimal priming of CD4+ T cells requires B cells over the first 2–3 days of infection and that this was independent of the production of antibody. T cells that were removed from PC-infected mice during the priming phase were fully functional and able to clear PC infection upon adoptive transfer into Rag1−/− hosts, but this effect was ablated in mice that lacked fully functional B cells. Our results indicate that T cell priming requires a complete environment of antigen presentation and activation signals to become fully functional in this model of PC infection.

Immune reconstitution inflammatory syndrome associated with pulmonary pathogens

“…Dectin-1 is involved in PCP-IRIS dependent lung injury, as antagonising dectin-1 signalling blocked the development of fungal IRIS [51]. B-cells are critical for effective CD4 + T-cell response to control Pneumocystis infection [49, 52]. However, there are no current data supporting a role for B-cells in regulating the pathology associated with PCP-IRIS [49].…”

New advances in understanding the host immune response to Pneumocystis

“…Additional patient groups at risk are patients with connective tissue disease with vasculitis or polymyositis/dermatomyositis. In addition treatments targeting B-cells in cancer or in autoimmune inflammation with anti-CD20 have been associated with Pneumocystis infection [9, 10]. This has been modelled in the mouse where anti-CD20 could perturb CD4 + T-cell priming and enhance susceptibility to infection [11].…”

“…Th2 responses to Pneumocystis drive an allergic reaction in healthy hosts. APCs = antigen presenting cells, Th = T helper, M1 = classically activated macrophages, M2 = alternatively activated macrophages [9, 10, 32, 34, 39]. …”

A Novel CD4+ T Cell–Dependent Murine Model of Pneumocystis-driven Asthma-like Pathology

“…1 T cells generate type II responses and facilitate production of protective anti-PC antibodies (29,30). One early effector function of CD4 1 T cells is to recruit eosinophils to the lungs, which subsequently reduces PC burden (31).…”