(1) Cell interactions
leading to germinal center development depend on the microenvironment
of lymphoid nodules (follicles).
(2) The requirements
for germinal center development include the following cellular
events:
a. Delivery
of antigen by antigen transporting cells (ATCs)
to the follicles from the subcapsular sinus in the lymph node
and from the marginal sinus in the spleen. Antigen is transported
to lymphoid nodules in the form of immune complexes (antigen-antibody
complex) for trapping on the surface of FDC dendrites; Thus,
antigen transport and antigen trapping
on FDCs are antibody dependent processes;
b. The FDC-reticulum,
a sponge-like three-dimensional network is formed by the interdigitation
of neighboring FDC dendrites. The FDC-reticulum provides an
important part of the microenvironment which brings together
FDCs and the FDC-retained Ag with Bm cells and T helper cells.
c. Selection
of specific B memory cells by the FDC-retained Ag (See
Fig. 4).
d. Delivery
of the FDC-retained Ag on the surface of iccosomes
to B memory cells (See Fig. 3).
e. Endocytosis
and processing of the iccosomal Ag by B memory cells
for presentation of Ag to T helper cells (See Fig. 4).
(3) The main function
of germinal centers is to produce Ag-specific B
memory cells and plasma cell precursors
that migrate to the LN medulla, splenic red pulp and to the bone
marrow where they complete their differentiation to plasma cells
for antibody production;
(4) The selection
of B memory (Bm) cells for production of more Bm cells in the
germinal center includes a process referred to as "affinity
maturation;" High affinity and Low affinity daughter
cells of Bm cells are made to compete for binding to the Ag on
FDCs. For these competing cells to stay alive they must be stimulated
by the FDC-retained Ag. Those not able to bind to the FDC-Ag will
die by the process termed apoptosis (genetically
programmed cell death). Low affinity cells will loose out and
become apoptotic. Tingible body macrophages phagocytose these
dying apoptotic B cells (see Fig. 5).