Germinal Center: Light and Apical Zones
The reactive (germinal) centers of follicles represent the B-cell zone of active antigen-dependent proliferation. Several functional regions are distinguished here, where B lymphocytes undergo sequential stages of development.
In the light zone, a "test" takes place for centroblasts and centrocytes (B cells after mutagenesis). This process is called positive selection. Follicular dendritic cells present uncleared antigens complexed with IgM to centrocytes. The key survival criterion is high affinity (binding strength) of the cell receptor for the antigen. Cells with low affinity (about 90% of the population) enter apoptosis and are subsequently phagocytosed by large macrophages. Surviving centrocytes either return to the dark zone for repeated mutations or transition to the next stage.
In the light apical zone, selected B cells transform into large, actively dividing B immunoblasts (plasmablasts) with pale nuclei and cytoplasm. It is here that crucial genetic rearrangement occurs—$C_H$ class switch recombination. The cell stops producing primary antibodies (IgM) and begins generating other classes, most commonly IgG, and less frequently IgA or IgE.
Follicular Mantle (Corona)
Following division in the apical zone, daughter cells migrate to the periphery of the follicle—the mantle zone (corona). In this B-cell zone, their pathways finally diverge into two directions:
- Formation of proplasma cells (plasmablasts). Some cells begin terminal differentiation to eventually become effector cells of humoral immunity—plasma cells.
- Generation of memory B cells. These cells differ from naive lymphocytes by bearing switched classes of immunoglobulins (IgG, IgA) on their membranes. Visually, they closely resemble small lymphocytes, featuring a hyperchromatic nucleus and a narrow rim of cytoplasm.
Memory B cells play a crucial role in the secondary immune response. Upon re-exposure to the same antigen, the body's reaction is faster and more robust due to a larger pool of pre-existing cells, their high affinity, and immunoglobulin gene amplification.
Tissues Outside the Follicle
The life cycle of lymphocytes is not limited to follicles. Development continues in deeper structures of the lymph node.
The paracortical zone is thymus-dependent (T-zone) and located between the follicles and the medulla. It houses T lymphocytes (helpers and cytotoxic T cells) undergoing antigen-dependent differentiation. The primary antigen-presenting cells of this zone are interdigitating dendritic cells, which present peptide antigens to T lymphocytes. Some B cells may pass through the paracortex in transit, entering the bloodstream directly.
Medullary cords are a B-cell zone located deep within the node. Proplasma cells "flow" here from the mantle to complete final maturation, as this process never occurs inside the follicle. The tissue of the cords contains mature plasma cells, proplasma cells, and typical macrophages.
Morphology and Identification of Plasma Cells
Plasma cells are the terminal stage of B lymphocyte development, serving as true cellular "factories" for antibody synthesis. These are large cells with an eccentrically located nucleus dominated by transcriptionally active euchromatin.
For protein synthesis, plasma cells require a robust intracellular apparatus. Their cytoplasm is packed with rough endoplasmic reticulum (rER), while antibody packaging is managed by a well-developed Golgi apparatus. Under light microscopy, the Golgi zone appears as a "hof" (clear pale area) next to the nucleus.
Histochemically, plasma cells are easily identified by stains targeting RNA, such as pyronin. Due to the massive number of ribosomes on the endoplasmic reticulum, the cell accumulates significant amounts of RNA, giving its cytoplasm a characteristic magenta color (pyroninophilia). These stained cells are localized predominantly in the medullary cords of the lymph node. Having fulfilled their function, they may remain there or leave the node via medullary sinuses and high endothelial venules.