Secondary Lymphoid Organs and Tissues
Secondary lymph follicle, H&E stain, 100x
B cell follicle
Description:
The B cell follicle in secondary lymphoid tissues and organs (e.g. lymph nodes, spleen, MALT) begins as a primary follicle composed of small mature naïve B cells enmeshed in a network of follicular dendritic cells (DCs) and a few macrophages. Once antigenic stimulation occurs, a germinal center appears, and is composed of B cells at various stages of differentiation, follicular DCs, helper T 2 (Th 2) cells, and an increased number of tingible body macrophages. These macrophages function to remove apoptotic B cells. The B cell follicle with a germinal center is referred to as a secondary B cell follicle. In addition to the germinal center it has a corona of small naïve B cells (follicular mantle, mantle zone) and in some areas (e.g. MALT), a prominent marginal zone, usually extending toward the mucosal surface, composed of large marginal zone B cells and some small memory B cells.
The morphologic appearance of the B cells in the germinal center is heterogenous:
Large non-cleaved B cell (centroblast)- Is 2-3 times larger than a normal small lymphocyte and the nuclear:cytoplasmic ratio is low but variable, and the cytoplasm is grey to light blue in color. The nucleus is round or oval and may be eccentric in location. The nuclear chromatin is immature with some clumping, and one or more nucleoli may be seen.
Large cleaved B cell (centroblast)- The appearance is the same as that of a large non-cleaved B cell except for cleavage of the nucleus.
Small cleaved B cell (centrocyte)- Is about 1 1/2- 2 times the size of a small lymphocyte, and the cytoplasm is more abundant with a grey to light blue color. The nucleus is cleaved and on fixed sections often appears elongated and twisted. The nuclear chromatin is more mature than in centroblasts, and nucleoli are less conspicuous.
Immunoblast- Is usually larger than centroblasts, the nucleus is eccentric in location with immature coarse chromatin with a variable degree of clumping, and nucleoli are prominent. The cytoplasm is deep blue (basophilic) in color.
These various morphologic subtypes of B cells tend to occur in specific areas of the germinal center. The centroblasts, both large cleaved and non-cleaved, occupy the zone proximal to the T cell zone, referred to as the "dark zone". The centrocytes (small cleaved B cells), occupy the more distal "light zone". Another zone, referred to as the "basal light zone" is located between the dark and light zones. Variable numbers of follicular dendritic cells, tingible body macrophages, and small lymphocytes (Th 2 cells) are also present in these areas.
Antigen-stimulated proliferation and somatic hypermutation occurs in the dark zone. Positive selection of high-affinity antigen-specific B cells occurs in the basal light zone as a consequence of interaction with antigen-antibody complement complexes on the follicular DCs. Cells not positively selected undergo apoptosis. On migration to the apical light zone, positively selected B cells further proliferate and class (isotope) switching occurs. B cell development within the germinal center is T cell (Th 2)-dependent.
Other important costimulatory factors include many cytokines (e.g. Il-2, Il-3, transforming growth factor β), and several cell-surface structures (e.g. CD40, CD19, CD21) that are crucial to the final development of memory B cells and pre-plasma cells after antigenic stimulation of näive B cells.
The Th 2 cells are antigen-specific, having been generated following antigen presentation by DCs with the same antigen that was responsible for the initial activation of the naïve B cells.
T cell zone
Description:
The T cell zone in secondary lymphoid tissues is less well defined. In lymph nodes it is located in the interfollicular areas, and usually in close proximity to the secondary B cell follicles. The appearance may be that of a well-defined nodule or may be diffuse. When it appears as a discrete nodule adjacent to the B cell follicle, the two are often referred to as a composite nodule. The cellular composition of the T cell zones is that of T cells enmeshed with interdigitating DCs and macrophages. In the spleen the T cells are located in the white pulp and are periarteriolar in distribution, and are also in close proximity to the B cell follicles. The appearance also may be nodular or diffuse.
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Charles
E.
Hess,
M.D.,FACP [more information]
Professor of Internal Medicine
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