Human immunity is a complex intricate battalion involving a
plethora of different cells cooperating to ensure the health of an individual.
Because of the diversity of immune cells, flow cytometry represents the best
method for studying functional and phenotypic properties of these cell subsets,
especially with the ever-expanding list of Cluster of Differentiation (CD) markers.
The immune system comprises of two distinct arms that are
inextricably linked; innate and adaptive immunity. The primary role of the innate
immune system is to provide a first line of defence by limiting the
colonization of invading pathogens until antigen-specific adaptive immune
responses are established.
Since we have previously discussed about the Cell-mediated adaptive
T cell immunity (https://www.linkedin.com/post/edit/6479961887206412288), this
article will mainly be discussing only on the adaptive humoral immunity B
cell and how flow cytometry plays a role. The hallmark of the
adaptive humoral immunity is the secretion of powerful multi-functional
antibodies that can eradicate bacteria either by neutralisation or promoting
opsonisation (phagocytosis/lysis).
The positive selection process of the B lymphoid progenitors occur
in the bone marrow where the cells’ surface B Cell Receptor (CD19) is
tested for its functionality to complete their maturation as naive B Lymphocytes.
The activation and subsequent maturation of the Naïve B cells is a
collaborative effort with the CD3+CD4+ T helper cells. After leaving the bone
marrow and upon encountering a deleterious antigen, the Naïve B cell will
capture that antigen and present it to a T helper cell via the MHC Class II
receptor. This collaboration will elicit an “activation” of the B cell to start
differentiating into 2 groups of cells, Plasma B cell or Memory B cell.
The CD138-CD38+ Plasmablast is an
immature precursor cell of the Plasma B cell. They have the capability to
secrete more antibodies than mature naïve B cells but less than plasma cells.
These cells have the flexibility to remain in this state for several days and
then either die or differentiate irrevocably into a plasma cell.
The CD138+CD38+ Plasma B cell will
start producing antibodies specifically targeting and eliminating the earlier
mentioned harmful pathogen. These Plasma B cells are permanently situated at
lymphoid organs such as bone marrow, spleen and lymph nodes to produce
antibodies to be released into the blood stream.
On the other hand, CD27+IgD- memory B cells
are localised in the germinal centers of the lymphatic system. They have one of
the longest shelf life in the immunity system like a strong seasoned
war-veteran. Their long-lived memory ability to jump-start the immune system to
mount a more rapid aggressive response than before against a re-encountered
antigen/pathogen is the cornerstone of vaccination. Acting as a recognition
center, they will detect any re-encountered pathogen and then phenotypically
modulate itself into the aforementioned plasma B cells, to produce immunologic
antibodies to eradicate the pathogen.So here is just a quick snapshot of how flow cytometry aids in studying the phenotypic difference in the various B cell subsets of the humoral adaptive immunity. However, understanding the above phenotypic information is just the tip of an iceberg. Understanding how drugs can affect these lymphocytic population in a diseased state is a long arduous process. Fortunately, the rapid advancement of flow cytometry will be the key to future drug discovery.
Disclaimer
1. Flow cytometric analysis images depicted in this article are for simplified illustration purposes only and shall not constitute to the exact analysis process
2. Information provided are for informal reading and not for official research usage
