In humans, hematopoietic stem cells (HSCs) continuously replenish all types of blood cells via a series of lineage restriction steps. This process begins with the production of common lymphoid progenitor (CLP) and common myeloid progenitor (CMP) cells, which subsequently differentiate further in response to various stimuli. CLPs further differentiate into specialized lymphoid cells that play critical roles in immunity.
Releated: Which cells have a myeloid lineage and how are they identified?
Cells of the lymphoid lineage include T cells and B cells, which are involved in adaptive immunity, and natural killer (NK) cells, which are part of the innate immune system.
To study how different lymphoid lineage cells function in health and disease, researchers must detect and quantify distinct cellular subtypes within a heterogeneous population. This can be achieved using antibodies for cell type-specific markers, allowing cells of interest to be visualized using techniques such as flow cytometry or immunohistochemistry (IHC).
Common marker classes include cluster of differentiation (CD) molecules, transcription factors, and chemokine receptors.
Terminally differentiated cells of the lymphoid lineage perform diverse roles in the immune response:
Although broad subsets of lymphoid lineage cells can be characterized using just one or two markers, identifying specific cell types within each subset often involves detecting defined marker groups.
All T cells express CD3, however, upon differentiation into cytotoxic T cells and helper T cells (Th), these cell subtypes express CD8 and CD4, respectively.
|
|
|
Helper T (Th) cells can be further sub-categorized based on the presence of additional markers. For example:
Tregs: IHC analysis of paraffin-embedded human tonsil using recombinant monoclonal antibody FoxP3 (D2W8E) Rabbit mAb #98377.
Like T cells, B cells can be identified using just a single marker—CD19. However, distinguishing between naïve B cells, plasma cells, and memory B cells involves detecting different marker combinations.
B cells can be sub-categorized based on the presence of additional markers, such as:
Like memory B cells, NK cells display differential marker expression according to cell function. Broadly, mature and immature NK cells can be identified using CD56 (also referred to as NCAM1) or NKG2A, but subsets with different functional profiles may express additional markers, including CD16, NCR, and TCR Vα24 Vβ11. Their functional state is also influenced by the expression of activating vs inhibitory receptors that modulate cytotoxic responses.
The following marker combinations can help identify functional NK cell subsets:
T cells become activated when their T cell receptor (TCR) recognizes and binds to a pathogenic antigen. Each cell-surface receptor has an affinity to a unique antigen, making T cells and the adaptive immune system highly specialized in antigen recognition.
Once the TCR binds an antigen, the T cell activates a series of internal signaling pathways that allow for the antigen recognition to be verified. Subsequently, the T cell will proliferate, expanding the pool of available cells that are specific for the harmful antigen, such as to different bacteria and parasites.
Blog: Faster Immuno-Oncology Research with Rapid T Cell Activation & Expansion
Understanding the molecular players involved in TCR signaling has been foundational to immuno-oncology, where therapeutics aim to enhance T cell activation and persistence. Identifying the resulting cell subpopulations—using the markers outlined above—is essential for characterizing immune responses in both basic research and therapeutic development.
To see key cell and functional state markers for immune cells, optimized for flow cytometry and IHC, download the immune cell markers guide:
Check out the additional blogs in our immunology series to learn more:
Updated May 2025. Originally published January 2022. 25-ICT-56550