Anatomy of germinal centers in mouse spleen, with special reference to "follicular dendritic cells"

Abstract

Lymphocyte proliferation in germinal centers (GC's) is thought to be triggered by antigen retained extracellularly on the surface of special "dendritic" cells. The anatomy and function of these cells have not been studied directly or in detail. We therefore examined mouse spleen GC's developing in response to sheep erythrocyte stimulation.We found that distinctive "follicular dendritic cells" (FDC's) were present in both the GC and adjacent mantle region of secondary follicles. The large, irregularly shaped nucleus, containing little heterochromatin, allowed for the light microscope (LM) identification of FDC's. By EM, the cell was stellate in shape sending out long, thin sheets of cytoplasm which could fold and coil into complex arrays. The processes were coated extracellularly by an amorphous electron-dense material of varying thickness, as well as particulates including variable numbers of virions. The FDC cytoplasm lacked organelles of active secretory and endocytic cells, such as well-developed rough endoplasmic reticulum (RER) and lysosomes. These anatomical features readily distinguished FDC's from other cell types, even those that were extended in shape.To pursue these descriptive findings, we injected three electron-dense tracers i.v. and sacrificed the mice 1 h-10 days thereafter. Colloidal carbon, colloidal thorium dioxide (cThO2), and soluble horseradish peroxidase (HRP) were actively sequestered into the vacuolar system of macrophages but were interiorized only in trace amounts by FDC's. Therefore, FDC's are not macrophages by cytologic and functional criteria. FDC's did display a unique property. Both colloidal carbon and thorium dioxide, which are nonimmunogens, could be visualized extracellularly on the cell surface for several days. The meaning of this is unclear, but the association of colloid with FDC's appeared to slow the movement of particulates through the extracellular space into the GC proper. FDC's were not readily identified in splenic white pulp lacking GC's. They must develop de novo then, possibly from novel dendritic cells that we have identified in vitro (Steinman, R. M., and Z.

Formation of lymph follicles and germinal centers in draining lymph nodes after local injection of phytohemagglutinin and lipopolysaccharide in mice.

“…On the basis of the present findings, it may be concluded that most of the new primary follicles are "de novo" formed at the site with no relation to the pre-existing follicles. Since many of the new primary follicles develop germinal centers in their medullary pole rather soon after their formation, the formation of the follicles appears to be accompanied by the acquisition of a capacity to develop germinal centers, possibly due to the development of follicular stroma with dendritic cells (WILLIAMS and NossAL, 1966;NOSSAL and ADA, 1971;HOEFSMIT, 1975;CHEN et al, 1978;HOEFSMIT et al, 1982). HOWever, the precise mechanism underlying the formation of new lymph follicles still remains unclear.…”

Decisions About Dendritic Cells: Past, Present, and Future

“…This was observed in vivo on "dendritic macrophages" (now called follicular dendritic cells, FDCs) (15). I did manage to show with Lei Chen that persistence in vivo is truly on the cell surface of the FDC (16,17). This meant that FDCs are very different from macrophages, on which I had failed previously to show retention of intact antigen and immune complexes in spite of large amounts of endocytosis (18).…”

Macaque Paneth Cells Express Lymphoid Chemokine CXCL13 and Other Antimicrobial Peptides Not Previously Described as Expressed in Intestinal Crypts

“…Furthermore, there might be differential expression of proteases that process CXCL13 in lymphoid tissue microcompartments, with a higher concentration of proteases in the surrounding paracortices relative to the inside the GCs. Such compartmentalization of proteases would be consistent with the ability of GCs to harbor immune complexes on FDC surfaces for long periods of time (25)(26)(27), and it is possible that FDCs also serve a depot function for CXCL13 as well. Regardless of the mechanism(s), the compartmentalization of CXCL13 within lymphoid tissue GCs is consistent with its role in bringing T fh cells, B cells, and DCs together.…”