Histopathology of a centroblast in follicular lymphoma

immunology Immunology is a branch of biology and medicine that covers the study of Immune system, immune systems in all Organism, organisms. Immunology charts, measures, and contextualizes the Physiology, physiological functioning of the immune system in ...

, a centroblast generally refers to an activated

B cell B cells, also known as B lymphocytes, are a type of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or inserted into the plasm ...

that is enlarged (12–18 micrometer) and is rapidly proliferating in the

germinal center Germinal centers or germinal centres (GCs) are transiently formed structures within B cell zone (follicles) in secondary lymphoid organs – lymph nodes, ileal Peyer's patches, and the spleen – where mature B cells are activated, prolifera ...

of a

lymphoid follicle A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that include ...

. They are specifically located in the dark zone of the germinal center. Centroblasts form from

naive B cell In immunology, a naive B cell is a B cell that has not been exposed to an antigen. These are located in the tonsils, spleen, and primary lymphoid follicles in lymph nodes. Once exposed to an antigen, the naive B cell either becomes a memory B c ...

s being exposed to

follicular dendritic cell Follicular dendritic cells (FDC) are cells of the immune system found in primary and secondary lymph follicles (lymph nodes) of the B cell areas of the lymphoid tissue. Unlike dendritic cells (DC), FDCs are not derived from the bone-marrow hem ...

cytokine Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

s, such as IL-6, IL-15, 8D6, and BAFF. Stimulation from

helper T cell The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considere ...

s is also required for centroblast development. Interaction between

CD40 Cluster of differentiation 40, CD40 is a type I transmembrane protein found on antigen-presenting cells and is required for their activation. The binding of CD154 (CD40L) on T helper cell, TH cells to CD40 activates antigen presenting cells and i ...

ligand on an activated helper T cell and the B cell CD40 receptor induces centroblasts to express

activation-induced cytidine deaminase Activation-induced cytidine deaminase, also known as AICDA, AID and single-stranded DNA cytosine deaminase, is a 24 kDa enzyme which in humans is encoded by the ''AICDA'' gene. It creates mutations in DNA by deamination of cytosine base, which ...

, leading to

somatic hypermutation Somatic hypermutation (or SHM) is a cellular mechanism by which the immune system adapts to the new foreign elements that confront it (e.g. microbes). A major component of the process of affinity maturation, SHM diversifies B cell receptors used t ...

, allowing the B cell receptor to potentially gain stronger affinity for an antigen. In the absence of FDC and helper T cell stimulation, centroblasts are unable to differentiate and will undergo CD95-mediated apoptosis. Morphologically, centroblasts are large lymphoid cells containing a moderate amount of

cytoplasm The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...

, round to oval vesicular (i.e. containing small fluid-filled sacs) nuclei, vesicular

chromatin Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important r ...

, and 2–3 small

nucleoli The nucleolus (; : nucleoli ) is the largest structure in the nucleus of eukaryotic cells. It is best known as the site of ribosome biogenesis. The nucleolus also participates in the formation of signal recognition particles and plays a ro ...

often located adjacent to the

nuclear membrane The nuclear envelope, also known as the nuclear membrane, is made up of two lipid bilayer polar membrane, membranes that in eukaryotic cells surround the Cell nucleus, nucleus, which encloses the genome, genetic material. The nuclear envelope con ...

. They are derived from B cells. Immunoblasts are distinguished from centroblasts by being B cell-derived lymphoid cells that have moderate-to-abundant

basophilic Basophilic is a technical term used by pathologists. It describes the appearance of cells, tissues and cellular structures as seen through the microscope after a histological section has been stained with a basic dye. The most common such dye ...

cytoplasm and a prominent, centrally located, trapezoid-shaped single

nucleolus The nucleolus (; : nucleoli ) is the largest structure in the cell nucleus, nucleus of eukaryote, eukaryotic cell (biology), cells. It is best known as the site of ribosome biogenesis. The nucleolus also participates in the formation of signa ...

which often has fine strands of chromatin attached to the nuclear membrane (‘spider legs’). In some cases, immunoblasts can show some morphologic features of

plasma cell Plasma cells, also called plasma B cells or effector B cells, are white blood cells that originate in the lymphoid organs as B cells and secrete large quantities of proteins called antibodies in response to being presented specific substances ca ...

s. Centroblasts do not express

immunoglobulin An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...

s and are unable to respond to the follicular dendritic cell

antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

s present in the secondary lymphoid follicles. However, they are able to promote the secretion of immunoglobulins though CD27/CD70 interactions. B cells begin expressing

CD27 CD27 is a member of the tumor necrosis factor receptor superfamily. It is currently of interest to immunologists as a co-stimulatory immune checkpoint molecule, and is the target of an anti-cancer drug in clinical trials. Expression During mo ...

at the beginning of the centroblast stage and lose the cell marker after differentiating into

centrocyte In immunology, a centrocyte generally refers to a B cell with a cleaved nucleus, as may appear in e.g. follicular lymphoma.Table 12-8 in: 8th edition. Centrocytes are B cells that are found in the light zones of germinal centers. Centrocytes are ...

s. CD27 is an important marker for germinal center formation in the lymphoid follicle and is produced by centroblasts interacting with CD28+ helper T cells. The production of the germinal center is important for the production of antibody secreting

s and memory B cells. After proliferation, centroblasts migrate to the light zone of the germinal center and eventually give rise to centrocytes.

References

{{reflist Lymphocytes