Iccosome Formation

According to the initial ideas on iccosome formation, iccosomes formed by the process of transformation (maturation) of FDCs. As shown in the scanning electron micrographs in Figs. 1 through 3, the filliform dendrites of FDCs (1) begin to develope beads (2) and soon (within 72 hrs in vitro) dendrites become completely beaded. The beads are coated with a very thin layer of immune complexes (ICs). This immune complex layer, however, is much less than the layers found on fully developed iccosomes between days 1 and 3 in vivo. To develop the thick immune complex layer on the surface of each iccosomes, it is thought, based on transmission electron microscopic evidence, that two cells are involved in this process. One is a FDC, like the one shown in Fig. 3 and the other is a dendritic cell with dendrites and veils of many shapes. The flattened veil-like processes have thick accumulations of imune complexes on their surface in defined areas (large spots). Beaded dendrites of FDCs bind to these spots and the beads are "loaded" with a thick layer of immune complexes.

For this proposed mechanism and illustrations refer below:

Iccosome Formation Diagram:

The above diagram depicts the theory of iccosome formation. In the left panel the electron micrographs supporting this theory are shown from "a" through "h." In "A" of the diagram two cells are shown to interact, an FDC and a cell with dendritic and veil-like processes. The second dendritic cell may be an ATC. ATCs were shown to have dendrites as well as some veils and are thought to be derived from veiled-like cells. According to the diagram, the beaded dendrites of a FDC bind to regions on the veils of this veiled / dendritic cell which are heavily coated with Ag-Ab complexes (brown). Areas of immune complexes on the electron micrographs (EM) in the left panel appear as black layers and the beaded dendrites as either structures colored yellow or pink. In "a," the pink colored beads appear to represent a series of interconnected beads on a beaded dendrite. The sections of the yellow beads may be from a number of different beaded dendrites. The green-colored cell processes belong to the ATC.

In electron micrographs of the FDC Network, cell processes appear to have extremely complicated patterns and show lots of convolutions. Filamentous dendrites and beaded dendrites have small round to oval profiles in cross sections. Veils, being sheet-like appear as elongated, more or less flattened profiles, much like the green colored processes in figure "a." Note that it is the green veil like processes that have relatively large areas of thick accumulations of Ag-Ab complexes that also bind complement (Ag-Ab-C'). On careful examination of the colored EM, one can easily get the impression that FDC "beads" bind to these accumulations of immune complexes. Figure "b" shows a complex colored area depicted in a simplistic form in diagram "B" and "C" above. Since immune complexes are typically bound to FDCs and ATCs via Fc receptors one may think of this process of the wrapping of FDC beads by the veiled processes as an Fc receptor- Ag-Ab-C' mediated process. The result is the wrapping of the beads with the flat processes into an immune complex rich package which after release measures about 0.3 microns in diameter. This is therefore an easily palatable size for germinal center B cells.

Figure "c, d, e, f, g, and h" on the left show this immune complex "loading" of beads and also show that the layer that represents the part of the veiled process disintegrate and can completely disappear, leaving an immune complex coated body (some) the ICCOSOME. Regarding the composition of the globular, black bodies in the centers of iccosomes, a close look at these with the electron microscope revealed a similar globular composition to that observed in the immune complex coat of the iccosomes. Consequently, these appear to represent complexed antigen. No lysosomes were observed in iccosomes, therefore, it is unlikely that these would represent processed antigen. These bodies are not membrane bound and probably just represent further loading of the antigen into the body of the ICCOSOME. Figures "e, f, and g" show good examples of these structures. A fully developed ICCOSOME is shown in figure "h" attached to a germinal center B cell. To see the process of endocytosis of an ICCOSOME by a germinal center B cell refer back to the alternative antigen transport pathway.

Refer to the "Humoral Response" link on the home page for Iccosome Endocytosis.