In 1875, a famous German scientist; Wilhelm Gottfried Waldeyer Hertz, described an immune cell with a large cytoplasm (the space within the cell aside from the nucleus), he was the first to name it the “plasma cell”. We now know that this large cytoplasm hosts a production line that is solely dedicated to antibody formation (up to 10,000 molecules per second per cell).
They account for less than 1% of all immune cells, and largely reside in the bone marrow, spleen, lymph nodes, mucous tissue as well as chronically inflamed tissues in disease conditions (such as the central nervous system compartment in multiple sclerosis). Nowadays, scientists use cell surface proteins (markers) to identify plasma cells rather than the morphological appearance. Among these markers are the CD138 and CD38, whilst losing the famous B-cell markers CD19 and CD20 expression. They are for all intents and purposes the grandmother or grandfather of the immune world overseeing immune responses at several levels in the human body.
Some of the plasma cells can live for a lifetime – the so called long-lived plasma cells; responsible for the long-lasting antibody response to different pathogens, vaccinations, as well as antibody mediated autoimmune diseases. Imagine a plasma cell that never forgets that you have MS?
How do plasma cells develop?
Plasma cells form from differentiated B-cells.
B cells originate from the bone marrow stem cells, once ready, these B cells travel to their duty watch point at lymph nodes and mucosal surfaces awaiting a potential invasion from a foreign pathogen which triggers B cell activation and differentiation into either plasma cell or a memory B cell.
Not all plasma cells are born equal. Some B cells quickly change into plasma cells that act like ‘rapid deployment troops’ and engage with invading organisms early. However, these plasma cells are short lived and fight only using IgM antibodies. More specialized plasma cells take days to fully develop but attack smarter and more specifically. What is impressive about these plasma cells is that they can survive for a life time. We have long standing immunity to many viruses and bacteria thanks to these long-lived plasma cells.
The Jobbing Plasma cell
The plasma cell sits at the end of the line in immune cell differentiation. Short living plasma cells undergo cell death within days, whilst long lived plasma cells have the capacity to survive and maintain their antibody production for a lifetime. Cells that are destined to survive migrate and settle primarily in the bone marrow, as well as secondary lymphoid tissues or mucosa, where they reside within a supporting survival niche.
Not surprisingly, survival niches can also occur in chronically inflamed tissues during infection but also in autoimmune diseases, such as MS. In MS, long lived plasma cells have been documented in the meninges and even within the brain/spinal cord parenchyma.
Problematic Plasma cells
Aberrant antibody production is a core feature of autoimmune diseases. Studies of different autoimmune conditions have shown that short and long lived plasma cells both contribute to organ injury.
Evidence for a prominent role of plasma cells in the pathology of multiple sclerosis is clear from earliest immunopathological studies, where plasma cells have noted within the brain of MS patients. In fact, one of the most characteristic phenomena that happens in nearly all MS is the oligoclional bands (OCBs) – ‘olig’ meaning few (see Figure below). When bands are seen exclusively in the CSF compartment as opposed to blood they are termed ‘intrathecal oligoclonal bands’, with the antibody production occurring exclusively in the CNS compartment. This antibody production is evidence that plasma cells do reside within the nervous system compartment and actively participate in the ongoing inflammation and tissue destruction. Specific IgM oligoclonal bands have also been noted with faster disease progression.
A congregation of B cells and plasma cell niches have been noted in the meninges coinciding with worse disability. These congregation can support a continuous long lasting damage, and encourage plasma cells to self potentiate setting up nodal points in the brain close to the activity.
How can plasma cells be targeted?
Lets not beat around the bush, there have been treatments for targeting plasma cells for more than two decades. That’s because there is a cancer of plasma cells which is deadly called Multiple Myeloma. The figure below shows how sophisticated these treatments really are.
We now have established targeted therapies for B cells in MS, ones targeting the plasma cells that play such a fundamental role is maintaining autoimmunity is long overdue.