Lung dendritic cells have a potent capability to induce production of immunoglobulin A

The mucosal immune system provides the first line of defense against inhaled pathogens in the lung. This system is largely mediated by immunoglobulin A (IgA) locally produced by plasma cells, which originate from homing IgA-committed B cells. It has not been determined what types of antigen-presenting cells (APCs) primarily induce B cell differentiation for IgA production in the lung. In addition, although mucosal dendritic cells (DCs) are functionally distinct from DCs in other tissues, it is unclear whether IgA-inducing capability differs between mucosal lung DCs (LDCs) and nonmucosal DCs. The present study was conducted to identify APCs principally responsible for IgA induction in the lung, and to determine potential differences in IgA-inducing capacity between LDCs and nonmucosal DCs. We measured immunoglobulin and cytokine production in a coculture system containing naive IgD(+) B cells, naive T cells from ovalbumin-specific T cell-receptor transgenic mice, and APCs including LDCs, alveolar macrophages (AMs), or spleen DCs (SDCs). LDCs induced significantly greater levels of IgA, IgG1, IL-6, and TGF-beta than AMs and SDCs, whereas no differences were found in the production of IgM or IgG2a. In addition, the IgA percentage of total class-switched immunoglobulin was highest in cocultures with LDCs (38.4%) when compared with those with AMs (15.1%) and SDCs (22.7%). Neutralizing TGF-beta, but not IL-6, significantly decreased IgA induction by LDCs and SDCs, but not by AMs. This study suggests that LDCs are the primary APCs introducing IgA to the lung, and have a more potent IgA-inducing capacity than nonmucosal DCs.