Decision letter: The HIV-1 envelope protein gp120 is captured and displayed for B cell recognition by SIGN-R1+ lymph node macrophages

Abstract

The human immune system contains many different cell types, which play specific roles in defending the body from invading pathogens, such as bacteria and viruses. For example, macrophages engulf and digest foreign material, whereas specialized B cells termed plasma cells produce molecules called antibodies that help to destroy specific pathogens. However, specific antibodies are only produced if naive B cells have already encountered the pathogen or its surface proteins. Attempts to improve how the immune system responds to the human immunodeficiency virus (HIV-1) have failed to control and prevent infection. One of the main components of many prospective HIV-1 vaccines is a protein called gp120, which is located on the surface of the virus. Specific B cells recognize this protein and can develop into plasma cells that produce antibodies against HIV-1. However, little is known about how these specific B cells initially get exposed to gp120. Park et al. injected gp120 into mice, and used sophisticated microscopy to track its movement through the animal. This revealed that gp120 is rapidly transported to nearby lymph nodes—organs that are spread throughout the body, and play an important role in maintaining the immune response. Specialized macrophages can then capture and deliver gp120 to other macrophages in the lymph node. These specialized macrophages serve as a gp120 reservoir and are located in part of the lymph node that is a bit like a traffic hub, in that other immune cells constantly pass through it. As such, B cells that specifically recognize gp120 have a high likelihood of encountering these gp120-bearing macrophages, thereby allowing the specific B cells to extract gp120, develop into plasma cells, and produce HIV-1 specific antibodies. Manipulating this macrophage network may help to optimize the antibody responses to gp120 and so, in the future, could provide a way of treating or preventing HIV-1 infections.