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research-review:aging-converts-innate-b1a-cells-into-potent-cd8-t-cell-inducers

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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.

Aging Converts Innate B1a Cells into Potent CD8+ T Cell Inducers

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

Summary (tldr;)

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.

Materials and methods

Flow cytometry

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.

Labelling

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 Fc (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:

Ligand short Full name Location Species specificity (used in this study) Short description
TNF-α Tumor necrosis factor alpha intra- human, mouse a pro-inflammatory cytokine
IFN-γ Interferon gamma intra- human, mouse a pro-inflammatory cytokine
CD19 B-lymphocyte antigen CD19 extra- human, mouse the antigen specific B-cell receptor
4-1BBL Induced by lymphocyte activation receptor ligand extra- human, mouse activator of CD137 (co-stimulatory receptor) on T-cells
CD86 Cluster of differentiation 86 extra- human, mouse activator of costimulatory receptors on T-cells which govern activation and survival
CD14
CD3
CD8
GrB
CD11b
CD138
CD43
CD69
CD120b
CD27 Cluster of differentiation 27 extra- human co-stimulatory receptor on B and T cells
IL-10 Interlukin 10 intra- human anti-inflammatory cytokine
CD5 Cluster of differentiation 5 extra- mouse marker for T-cells and in mice B1a cells
CD119 IFN-γ receptor 1 extra- mouse stimulated by IFN-γ
CD23 Fc receptor CD23 extra- mouse low affinity receptor for the constant region of certain antibodies
CD21/CD35

Sorting/Detection

In vitro stimulation

In vivo antigen specific stimulation

Results

Aging milieu activated B1a cells

Aging converts B1a cells into 4BL cells

Myeloid cells induce the generate of 4BL cells that drive antigen specific cytotoxic effects

Putative mechanism of myeloid induction

Discussion

research-review/aging-converts-innate-b1a-cells-into-potent-cd8-t-cell-inducers.1573182060.txt.gz · Last modified: 2019/11/08 03:01 by marcos