Lymphocytes: Overview, Quantity, Morphology

Overview

Origin

Peripheral blood lymphocytes originate either in the bone marrow or thymus.

In healthy dogs and cats, circulating lymphocytes (Fig. 9-1a, Fig. 9-1b, and Fig. 9-1c) are approximately 70% thymus derived (T-lymphocytes) and approximately 30% bone marrow derived (B-lymphocytes).

Figure 9-1a. Normal lymphocytes. Lymphocytes in the dog and cat are the same size or smaller than a neutrophil. Canine lymphocytes have a scant amount of light blue cytoplasm with an eccentric, round, nucleus that has a dark, smooth chromatin.

Figure 9-1b. Normal lymphocytes. Lymphocytes in the dog and cat are the same size or smaller than a neutrophil. Canine lymphocytes have a scant amount of light blue cytoplasm with an eccentric, round, nucleus that has a dark, smooth chromatin.

Figure 9-1c. Normal lymphocytes. Lymphocytes in the dog and cat are the same size or smaller than a neutrophil. Feline lymphocytes are similar to those in the dog (A and C 100x, B 120x).

Unlike granulocytes and monocytes, which move unidirectionally from bone marrow to blood to tissue, blood lymphocytes recirculate. The pattern is blood to lymph node to lymph and back to blood.

> Transit time in the blood during each circuit is estimated to be 8 to 12 hours.

Recirculating lymphocytes are long-lived cells which survive for months to years.

Function

Lymphocytes are the cells of the specific immune system.

> B-lymphocytes differentiate into plasma cells (Fig. 9-2) which produce antibodies (humoral immunity).

> T-lymphocytes are responsible for cellular immunity through the formation and release of molecules known collectively as cytokines.

Figure 9-2. Plasma cells. B-lymphocytes differentiate into plasma cells. These cells have an eccentric round nucleus, clumped chromatin, and blue cytoplasm that contains a focal clear zone (100x).

Peripheral blood lymphocytes serve as the memory cells of the immune system.

> As they recirculate, lymphocytes monitor for the presence of antigens to which they have been previously sensitized.

> When lymphocytes activated by such contact enter lymph nodes, they can initiate both the cellular and humoral immune response through selective clonal expansion.

Quantity

Lymphopenia

Lymphopenia is a reduction in the number of circulating lymphocytes.

Causes of lymphopenia include:

 > High circulating levels of glucocorticoids (stress, Cushing's disease).

• Degree of lymphopenia is mild
• counts between 750/µl and 1000/µl.
• Counts lower than 750/µl suggest other causes.

> Disruption of lymphatic recirculation (chylous effusions).

• Counts can be very low (200/µl or less).
• Often accompanied by decreased plasma protein.

> Lymphosarcoma

• Lymphopenia can result from the inability of recirculating lymphocytes to migrate through effaced nodes.
• Lymphopenia is as common in cases of lymphosarcoma as is lymphocytosis.

Lymphocytosis

Lymphocytosis is an increase in the number of circulating lymphocytes.

Causes include:

> Excitement (physiologic lymphocytosis in cats only)

• Physiologic lymphocytosis results from increased circulating epinephrine which causes increased blood flow and washes marginated lymphocytes back into circulation.
• Lymphocyte counts can reach up to 20,000/µl.
• Lymphocyte morphology and red cell measures are normal.

 > Antigenic stimulation

• Inflammatory conditions are often associated with antigenic stimulation. Over time, lymphocytosis and elevated globulins may result.
• Many lymphocytes are reactive (see morphology below).
• Vaccinations may cause lymphocytosis, often with many reactive forms.

> Lymphosarcoma/lymphocytic leukemia

Lymphocytosis is generally a late event.

Usually accompanied by marked nonregenerative anemia.

Thrombocytopenia and neutropenia may also be present.

Large numbers of circulating lymphocytes may be neoplastic lymphoblasts large (20 μ or more) cells with lacy nuclear chromatin and prominent large nucleoli.

Morphology

Normal

Normal lymphocyte morphology is similar in dogs and cats.

Features of normal lymphocytes include (see Fig. 9-1a, Fig. 9-1b, and Fig. 9-1c):

• Size - 9 - 12 µ
• Nucleus - round, eccentric, clumped chromatin
• Cytoplasm - scant rim, pale blue

Activated (Antigen-Stimulated) Lymphocytes

Antigen-stimulated lymphocytes are also known as reactive lymphocytes, immunocytes, or blast transformed lymphocytes.

Reactive lymphocytes represent an appropriate response to antigenic stimulation (Fig. 9-3a and Fig. 9-3b).

Figure 9-3a. Reactive lymphocytes. Antigenic stimulation produces morphologic changes in canine lymphocytes. Reactive lymphocytes are larger than a neutrophil, vary in size, and have dark blue cytoplasm. Nuclei are rounded with a reticular chromatin and remnants of nucleoli (100x).

Figure 9-3b. Reactive lymphocytes. Antigenic stimulation produces morphologic changes in feline lymphocytes. Reactive lymphocytes are larger than a neutrophil, vary in size, and have dark blue cytoplasm. Nuclei are rounded with a reticular chromatin and remnants of nucleoli (100x).

Morphologically similar in dogs and cats.

Antigen-stimulated B cells cannot be differentiated from antigen-stimulated T cells on the basis of morphology. However, differentiated B-lymphocytes are morpholicaly distinct and are recognized as plasma cells (Fig. 9-2).

Morphology of reactive lymphocytes is highly variable from cell to cell. In general, features include:

• Size - 15 - 20 μ
• Nucleus - large, reticular chromatin pattern. Nucleoli may be present.
• Cytoplasm - abundant, light to deep blue. Pale perinuclear zones may be present.

Atypical Lymphocytes

Atypical lymphocytes are an abnormal finding (Table 9-1)

Atypical lymphocytes may be present in both infectious and neoplastic diseases and are therefore a nonspecific finding (Fig. 9-4, Fig. 9-5, and Fig. 9-6).

Figure 9-4. Canine atypical lymphocyte. The lymphocyte is larger than a neutrophil with a cleaved irregular nucleus that has reticulated chromatin (100x).

Figure 9-5. Feline atypical lymphocytes. The cells are round with abundant blue cytoplasm, large discrete irregular purple cytoplasmic granules, and oval nuclei with clumped chromatin. These cells are typical of large granular lymphoma in the cat (100x).

Figure 9-6. Canine lymphocytic leukemia. Numerous large lymphocytes are noted that have an abundant light blue cytoplasm, reticulated chromatin, and prominent nucleoli (100x).

Morphologic features include:

• Usually large
• Indented or clefted nuclei (termed Reiderform)
• Unusually large cytoplasmic azurophilic granules.