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Microscopic appearance of the blood.

Lymphocytes are types of leukocytes (white blood cells) that represent the primary cells of the immune system. All leukocytes are classified into granulocytes and agranulocytes, and lymphocytes belong to the agranulocyte group.

Lymphocytes occur in large numbers in blood, lymph and lymphoid tissues, such as the thymus, lymph nodes, spleen, and appendix. They account for about 30% of all leukocytes found in blood and are the most common agranulocytes. Although uniform in appearance, lymphocytes differ in their functions and are grouped accordingly into T lymphocytes (T cells), B lymphocytes (B cells) and natural killer (NK) cells.

Lymphocytes are the main functional cells of the immune system, being responsible for production of antibodies, direct cell-mediated killing of virus-infected and tumor cells, and regulation of the immune response.

This article will discuss the histology and function of lymphocytes.

Key facts about the lymphocytes
Definition Primary cells of the immune system that belong to the agranulocyte group of leukocytes
Size Small: 6 to 15 µm in diameter
: 15 to 30 µm in diameter
Structure Small:
- Large spherical nuclei with condensed chromatin
- Fewer organelles (mitochondria and ribosomes) and small Golgi apparatus
- Sparse azurophilic granules

- Large indented nucleus
- More organelles, developed Golgi apparatus, small rough endoplasmic reticulum
- More cytoplasm and azurophilic granules
Classification B lymphocytes
T lymphocytes
Natural killer (NK) cells
B lymphocytes Department: Humoral immunity

: Plasma cells and memory cells

: Antibody secretion, antigen presentation, acquired immunity
T lymphocytes Department: Cell-mediated immunity

: Cytotoxic T cells, helper T cells, regulatory (suppressor) T cells

: Cell-mediated killing of infected or neoplastic cells, induction/suppression of the immune system
Natural killer (NK) cells Department: Innate immunity

: Cell-mediated killing of infected or neoplastic cells
  1. Lymphocyte structure
  2. Classification
    1. B lymphocytes
    2. T lymphocytes
    3. Natural killer (NK) cells
  3. Clinical relations
    1. Lymphoma
  4. Sources
+ Show all

Lymphocyte structure

Lymphocytes are typically small, however they have a wider range of sizes compared to other leukocytes. The lymphocytes found in lymphatic tissue can be classified as small or large, ranging from 6 to 30 µm in diameter. Mature lymphocytes that circulate in the blood are mainly small and have a size similar to erythrocytes, averaging around 6 to 15 µm in diameter.

On light microscopy, small lymphocytes have large spherical nuclei with condensed chromatin. The nucleus is surrounded by a thin pale blue rim of minimal amount of cytoplasm. Generally, no cellular organelles are visible in these lymphocytes, other than the occasional azurophilic granule. Large lymphocytes have a larger nucleus that is indented, giving it a kidney-shaped appearance. These lymphocytes also have more cytoplasm with greater amounts of azurophilic granules. The azurophilic granules stain intensely due to the abundance of lysosomal enzymes, giving lymphocytes their dotted appearance.

On transmission electron microscopy (TEM), small lymphocytes show sparse organelles, such as mitochondria, polysomes and free ribosomes. In addition, this technique can also reveal a pair of centrioles and a small Golgi apparatus in the center of the lymphocyte, near the indentation of the nucleus. When observed by TEM, large lymphocytes have a more developed Golgi apparatus and a greater number of mitochondria and ribosomes, as well as a small rough endoplasmic reticulum.

Check out our study unit below for a quick reminder about the basics of cell structure, histological staining and slide examination. We have learning materials that you’ll find useful when identifying lymphocytes!


Lymphocytes are subdivided into 3 functional groups based on their distinctive surface molecules called cluster of differentiation, or CD markers.

These groups include: 

  • B lymphocytes (B cells)
  • T lymphocytes (T cells)
  • Natural killer (NK) cells

B lymphocytes

B lymphocytes (B cells) originate and mature in the bone marrow, from which they derive their name. B cells are involved in humoral immunity, as they produce antibodies in response to foreign antigens (fragments or whole bacteria, viruses and parasites). The antibodies produced by B cells serve to bind onto and neutralize these pathogens, as well as to mark them for later cell-mediated killing carried out by T and NK cells.

Additionally, B cells act as antigen-presenting cells (APC). These kinds of cells express a foreign antigen on their cell surface bound to a major histocompatibility complex (MHC) protein, in a process called antigen presentation. Aside from B cells, macrophages and dendritic cells also take part in antigen presentation, and they all display the antigens to a subtype of T cells called helper T cells, which will be discussed later.

B cells arise from pluripotent hematopoietic stem cells. After maturing into competent B cells, they are released into the bloodstream and aggregate in the lymph nodes and lymphoid tissue of the respiratory tract, gastrointestinal tract, and spleen.

B cells are further classified into plasma cells and memory B cells.

  • Plasma B cells produce antibodies that bind onto pathogens as well as infected or neoplastic cells, marking them for later cell-mediated killing.
  • Memory B cells serve to memorize every specific antigen that was encountered, in order to mount a strong and rapid immune response the next time that same pathogen is encountered again. This is the basis of acquired immunity as well as the pillar for vaccine efficacy.

T lymphocytes

T lymphocytes (T cells) are involved in cell-mediated immunity in response to intracellular pathogens (bacteria, viruses, parasites), tumor cells and, at times, surgical implants.

T cells originate from the same pluripotent hematopoietic stem cells as B cells and other blood cells, which are located primarily in the bone marrow. However, the precursors of T cells migrate from the bone marrow into the thymus, where they differentiate and mature into functional T cells, which is how they got their name.

In the thymus, the maturing T cells undergo an extensive selection process in which most of them are destroyed as soon as they develop, and only a fraction of these cells mature and migrate to the bloodstream. This happens to ensure that only properly-functioning T cells survive. A dysfunction in this selection process is the basis of some autoimmune diseases, in which T cells misdirect their response to healthy cells and tissues of the body.

There are 3 major types of T cells with different functions that are mediated by their surface molecules:

  • Cytotoxic T cells, characterized by CD8+ surface molecules, are the primary effectors of the cell-mediated immune response. They recognize and bind to antigens of virally infected or neoplastic host cells. When a cytotoxic T cell binds to the target infected or neoplastic cell cell, it secretes lymphokines and perforins that cause its lysis. In some cases, surgical implants can be targeted in this same manner, which is one of the causes of transplant rejection.
  • Helper T cells, characterized by CD4+ surface molecules, serve to recognize foreign antigens presented to them by antigen-presenting cells (such as macrophages, B cells and dendritic cells). When a helper T cell binds to the presented antigen, it gets activated and starts producing cytokines that influence the activity of other immune cells. These cytokines stimulate the proliferation and differentiation of more helper T cells, as well as the differentiation of B cells into plasma cells.
  • Regulatory (suppressor) T cells are also characterized by CD4+ surface molecules, but they carry out the opposite function of helper T cells. Regulatory T cells suppress the immune response by suppressing the activity and differentiation of helper T cells and B cells.

Identify the different blood cell types under the microscope with this fun quiz!

Natural killer (NK) cells

Natural killer (NK) cells originate from the same pluripotent hematopoietic stem cells as T and B cells. They mainly differentiate and mature in the bone marrow, but also in secondary lymphoid tissue such as lymph nodes, spleen, tonsils, and thymus.

NK cells are the largest of the lymphocytes, averaging around 15 µm in diameter. These cells often have large granules in their cytoplasm that are easily seen by light microscopy, which is why they are also called large granular lymphocytes (LGLs).

NK cells are involved in the innate immune system and are responsible for killing certain virus-infected cells and several types of tumor cells. The NK cells are called ‘natural killer’ because, unlike the cytotoxic T cells, they do not need to be activated in order to carry out the killing of another cell, allowing for a much faster immune response.

The NK cells recognize the infected and neoplastic cells by detecting changes in or lack of the major histocompatibility complex (MHC) proteins that are normally expressed by all cells. Once they find a target, the NK cells release cytotoxic granules, which destroy the infected or neoplastic cell, or release cytokines that trigger the apoptosis of the cell. Additionally, NK cells secrete interferon-gamma (IFN-γ), a cytokine that is crucial for innate and acquired immunity against viral, and some bacterial and protozoan infections.

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