Lee-Chang C, Bodogai M, Moritoh K, et al. Aging Converts Innate B1a Cells into Potent CD8⁺ T Cell Inducers. J Immunol. 2016;196(8):3385-3397. doi:10.4049/jimmunol.1502034

This article will be discussed on November 14th at Biotech without Borders as part of the Deep Dive series.

In the context of the review which this paper is paired with for Deep Dive, this is an example of “altered intercellular communication”. Specifically this is about the immune system behaving differently over time that is referred to as immunosenecence.

This is a follow up paper to an earlier observation by the group that a subset of B cells that accumulate in elderly mammals (4-1BBL⁺). These cells are shown to induces anti-tumor CD8⁺ T-cells in mice. In this report, they investigate a mechanistic hypothesis as to how these cells develop during aging. Through their experiments they demonstrate that certain cytokines produced by aging myeloid cells induce a subset of B cells which can activate CD8⁺ T-cells in an antigen dependent manner to express GrB. They also show limited data which support that a similar subset of B cells in humans also respond in the same way to aging myloid cells and induce a similar subset of T-cells.

This is method which is heavily relied on in immunology. It relies on a microfluidic device known as a flow cytometer and a variety of fluorescent antibodies for various intracellular and extracellular molecules. Immune cells can be identified by the various molecules they express. With flow cytometry cells prepared from various sources into a single cell suspension can be counted and even sorted for collection.

Antibodies recognize a specific molecular pattern which is referred to as its ligand (similar to the terminology to receptors). In order to differentiate cells, a fluorescent pigment molecule (fluorophore) is attached to an antibody specific for a identifying molecule. This molecule could be a inside the cell (intracellular) or outside the cell (extracellular). Often intracellular ligands are secreted signalling molecules, but could also include enzymes, transcription factors, the intracellular portions of receptors etc. etc. Extracellular ligands are cell surface features, most often receptors. Before cells are stained they must have all non-specific binding patterns blocked. This is especially important in immunology where many cells are able to bind the F_c (constant) region of antibodies. To access intracellular ligands, cells are fixed and permeabilized.

It helps to know what the various ligands are so here's a table: