Morphology and clonal organization
Lymphocytes are small, round cells with a diameter of 6–8 µm. A distinctive feature of their structure is a large, kidney-shaped nucleus occupying almost the entire volume of the cell, and sparse cytoplasm practically lacking granules. It is important to understand that their appearance does not allow one to distinguish one lymphocyte population from another, or even from hematopoietic stem cells in a state of functional rest.
The uniqueness of classical T and B lymphocytes lies in their clonal structure. An antigen-recognizing receptor of strict specificity is expressed on the surface of each such cell. Upon contact with an antigen, the cell is activated and begins to divide. As a result, a clone is formed — a multitude of cells with absolutely identical receptors copied from the original "mother" cell. At the same time, lymphocytes from different clones always differ from each other in the structure of their receptor apparatus.
Main lymphocyte populations
There are three main groups of lymphoid cells, differing by maturation site, receptors, and functions:
- B lymphocytes. They develop in the bone marrow (in birds, in the bursa of Fabricius). They recognize free antigens using the B-cell receptor (BCR). Their key surface markers are CD19 and membrane immunoglobulins. Their proportion in the blood is 10–18%. The main task of B cells is to serve as precursors for antibody-producing cells.
- T lymphocytes. Their site of differentiation is the thymus. These cells recognize not free antigen, but peptide or lipid fragments presented on major histocompatibility complex (MHC) molecules. The main marker complex is CD3–TCR. T lymphocytes account for 65–75% of the blood lymphocyte pool, and they are capable of active recirculation. The population includes precursors of helpers (CD4+) and cytotoxic lymphocytes (CD8+).
- Natural killer (NK) cells. Unlike T and B cells, they lack specific receptors for individual antigens and belong to innate immunity factors. They recognize stress molecules and MHC on target cells. They mature in the bone marrow, constitute 10–20% of blood lymphocytes, and do not recirculate. The main marker is CD56. They perform a cytotoxic function.
Early ontogeny and differentiation
All lymphocytes originate from the hematopoietic stem cell (HSC). Maturation is regulated by specific transcription factors and is accompanied by a change in surface markers on the membrane:
- An early lymphoid progenitor (ELP) is formed from the stem cell.
- Under the influence of differentiation factors Ikaros and PU.1, it transitions to the stage of the common lymphoid progenitor (CLP).
- Further pathways diverge. Development along the B-lineage requires factors Ikaros, E2A, EBF, Pax5, and Sox4 (forming a Pro-B cell). The T-lineage requires the participation of Notch1, GATA-3, Runx1, and c-Myb (forming a Pro-T/DN1 cell). Differentiation into NK cells is driven by Id2 and IRF1 factors.
Special case: interaction with superantigens
Usually, the T-cell receptor (TCR) recognizes a peptide inside a special binding cleft. However, there are superantigens (e.g., staphylococcal exotoxin SEB) that bind in a non-standard way: to the external, lateral surface of the TCR $\beta$-chain and simultaneously to the MHC-II $\alpha_1$-domain on the antigen-presenting cell.
Such binding causes massive polyclonal activation. Not single specific clones, but generally all CD4+ T lymphocytes carrying certain $\beta$-chain families (e.g., V$\beta$7 and V$\beta$8) enter the reaction. As a result, a colossal number of T helpers (up to 20–30%) are activated, leading to an inadequate release of cytokines — a cytokine storm.
Hyperactivation is followed by massive death (apoptosis) of the responding clones. It is worth noting that cytotoxic CD8+ T lymphocytes do not participate in this reaction because their receptors do not have an affinity for MHC-II molecules.
Briefly: answers to topical questions
What are the morphological features of lymphocytes under light microscopy of a blood smear?
Under light microscopy of a blood smear, lymphocytes are represented predominantly by small and medium round cells.
- Small and medium lymphocytes — have a large, hyperchromatic (intensely stained) round or kidney-shaped nucleus occupying almost the entire cell. The cytoplasm forms a narrow rim with basophilic staining and lacks granules.
- Large lymphocytes — reach a size of 12–15 µm and account for 5–10% of the total number.
- Natural killers — are an exception and look like large granular lymphocytes.
Which specific cytokines are massively secreted by T helpers during the development of a cytokine storm caused by superantigens?
During the development of a cytokine storm caused by exposure to superantigens, polyclonal activation of T lymphocytes and excessive production of pro-inflammatory cytokines occur. Specific cytokines mentioned in the source include:
- TNF-α — tumor necrosis factor alpha;
- IL-1 — interleukin-1;
- IL-6 — interleukin-6;
- $\gamma$-interferon — gamma-interferon.
T lymphocyte activation occurs without conventional antigen processing.
To easily remember the primary maturation organs of the main lymphocytes, focus on their first letters in English: B lymphocytes — Bone marrow, T lymphocytes — Thymus.
Class and exam questions
Can a T lymphocyte be distinguished from a B lymphocyte under a light microscope?
No, morphologically all lymphocytes look identical — as small round cells with a large kidney-shaped nucleus and a narrow rim of cytoplasm. They can be identified only by the presence of specific surface CD markers.
Which cells combine features of innate and adaptive immunity?
This "transitional" group includes NKT cells, $\gamma\delta$ T cells, B1 lymphocytes, and marginal zone B cells of the spleen. They are traditionally considered within adaptive immunity due to their common origin with classical lymphocytes.
Why do superantigens not activate CD8+ cytotoxic T lymphocytes?
Binding of a superantigen requires its interaction with the MHC-II molecule on the antigen-presenting cell. CD8+ T lymphocyte receptors have no affinity for MHC-II, so they are not involved in polyclonal activation.
What else to study on this topic
- Detailed B-cell membrane phenotype: the role of CD20, CD21, chemokine receptors, and adhesion molecules
- Structure and functions of the CD3–TCR receptor complex in T lymphocytes
- Changes in CD markers at the stem cell (HSC), ELP, and CLP stages
- Stages of apoptosis (deletion) of T-cell clones after superantigen exposure: acute, subacute, and chronic
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