What are Naïve Cells? Naïve T Cell, Naïve B Cell, and How to Isolate Naïve Lymphocytes
August 2020 Share
What Is a Naïve Cell?
Lymphocytes are a type of white blood cell that carry out effector functions against foreign particles that could cause an infection. They play an integral role in human adaptive immunity due to their antigen-specificity.
Before lymphocytes are activated by their unique antigen stimulus, they circulate the bloodstream as naïve lymphocytes with specialized receptors on the hunt for foreign pathogens. Divided into T and B cell subtypes, lymphocytes are specially designed to recognize invading pathogens and carry out different functions to destroy them. Once a surface receptor on the naïve cell is triggered by binding to an antigen, a targeted immune response can begin against the potential infection.
Naïve T Cells
T cells are a critical part of the adaptive branch of the immune system. Each T cell is equipped with a unique T cell receptor (TCR) generated through DNA rearrangements during maturation.
TCR binds to a single antigen target from a specific foreign pathogen presented by an antigen-presenting cell (APC) that activates a signaling cascade, resulting in an inflammatory response. T cells can also recognize cancerous cells and, once activated, have anti-tumor or cytotoxic abilities.
All T cells begin as stem cells in the bone marrow. These undifferentiated cells migrate from the bone marrow into the thymus, where they acquire identifying surface markers, such as CD3, CD4, CD8, and TCR. T cells are thus named because of their development period within the thymus.
Moving through differentiation, selection, and proliferation, the T cell development process results in T cells ready for circulation within the peripheral blood. These fully-equipped, unactivated T cells are naïve T cells.
Naïve T cells will circulate through the blood and lymphatic system until becoming activated by encountering an APC with a corresponding antigen. Antigens play a significant role in T cell activation and can initiate a full-scale immune response.
Many naïve T cells will remain in the bloodstream and lymphatic tissues their whole existence, never being activated by their unique trigger. Only one in every 100,000 naïve T cells will become activated, with this rate varying as humans age.
Naïve B Cells
Similar to T cells, B cells also begin as stem cells that undergo differentiation and subsequent activation by a unique antigen. B cells are bone-marrow-derived cells that express the B cell antigen receptor, or BCR. This receptor allows B cells to bind to a specific foreign antigen.
Often, the final stage of B cell development occurs in the spleen, where they develop into naïve B cells. These mature but inactive B cells then travel via the bloodstream to the secondary lymphoid organs, SLO.
Naïve B cells are more likely to encounter an invading virus or pathogen because of the distinct and specialized location of the SLOs perfectly situated at common entry points to the body. It is in the SLOs that the human immune system fights off infection. Once Naïve B cells are activated, they secrete antibodies to neutralize the exposure.
How Are Naïve T Cells Activated?
Antigen-presenting cells are key in naïve T cell activation. APCs will circulate the body, gathering up pieces of foreign cells in the form of antigens and carrying them back to the SLOs.
Once the APC comes in contact with a T cell expressing the corresponding TCR, the antigen-MHC complex will bind to the TCR and initiate the signaling cascade. This alone is not sufficient to activate most naïve cells and can cause a cell to become anergic, or unable to carry out an immune response.
To successfully catalyze an inflammatory reaction and achieve naïve cell activation and expansion, three binding signals must occur at the same time: TCR binding, cytokine signaling, and the binding of a co-stimulatory molecule, such as CD28.
Cytokines and co-stimulatory molecules bolster the effects of TCR binding to the antigen in order to trigger an activation cascade. Once naïve cells are activated by the APC, the cells differentiate into effector cells and begin the process of nullifying the potential infection.
Antibody Synthesizing Capabilities
B cells can be activated by direct binding to an antigen. Once a naive B cell recognizes its target antigen, they form germinal centers with the help of CD4 helper T cells.
In the germinal center early stage antibody-secreting B cells undergo isotype switching and transition into a plasma cell. Antibody production by B cells can quickly neutralize a potential infection. Once the infection is neutralized, B cells can become memory B cells, which exist in small numbers in the case of re-infection.
Where Are Naïve Cells Found?
Naïve cells are derived from stem cells, which are generated within the bone marrow. Naïve T cells, or thymus cells, are stem cells that spend their maturation phase in the thymus and move into the lymphatic system.
Naïve B cells, or bone marrow cells, mature in the bone marrow before they are released into the secondary lymphoid organs, including the lymph nodes, spleen, mucosal tissues, and lymphatic vessels.
Naïve vs. Effector Cells
For T cells to acquire their designated functions, they must first be activated by complementary APC and co-stimulatory molecules. Naïve T cells differ phenotypically from activated effector cells by expressions of many surface receptors but are most commonly distinguished by the absence of the activation protein, CD25.
Naïve cells can still differentiate into another type of T or B effector cell. Many effector cells are considered “terminally differentiated,” meaning they will never change into another cell type and have reached the end of their differentiation and maturation process. They are fully activated to carry out their immune functions, and most will die once this function is no longer needed.
What Cell Populations Are Used in Cell Therapy?
Numerous immune cells including T cells, B cells, and NK cells are the most common starting material in adoptive cell therapy treatments. Isolating naïve cells from the periphery can be tedious, as they can be elusive targets with limited distinctions and are often isolated from apheresis blood products called leukopaks.
Other Applications of Naïve Cell Isolation
Naïve cells are particularly interesting in immunology research due to their unique ability to differentiate into multiple effector subsets. This flexibility makes them promising material for researching the effects of novel diseases on immune systems and vaccine efficacy.
In addition to vaccine development and clinical disease studies, naïve cells can provide insight into the causes of autoimmune deficiencies and the immune cell differentiation process via antigen recognition and activation.
What Is the Best Way to Isolate Naïve Cells?
Isolating pure cell populations from peripheral blood using standard venipuncture methods is often not a scalable source for the demands of cellular research. Leukopaks, an apheresis product, is a human peripheral blood mononuclear cells (PBMC) rich material that can be preserved and shipped as a ready source of cells to address the scalability discrepancy of cell population demands.
A common research method is to isolate only the PBMCs or agranulocytes from the leukopak, resulting in a solution rich with white blood cells. This process is composed of several cell isolation techniques that utilize magnetic beads, fluorescence, density or centrifugation, and filtration.
Akadeum has developed an innovative method for isolating single-cell populations through negative selection and without a buffy coat, leaving desired cells untouched by the isolation process. This is possible due to the natural buoyancy of Akadeum’s engineered Buoyancy Activated Cell Sorting BACS™ Microbubbles.
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