Researchers identify possible precursors of lymphoid tissue cellular network
Japanese researchers have identified a subset of cells they believe may induce the formation of a network of follicular dendritic cells (FDC) in the spleen and lymph nodes.
A recent paper published by Hiroshi Ohno and colleagues at the RIKEN Research Center for Allergy and Immunology, Yokohama, suggests that in the mouse, spleen cells expressing the cell surface marker proteins CD35, involved in processing and clearance of immune complexes, and B220, found on almost all immune system cells, can induce the formation of these networks and ultimately lymphoid follicles1 (Fig. 1).
These so-called FDC form a reticular network of cells in the spleen and lymph nodes that trap immune complexes of antibodies, antigens and associated molecules. The network plays a critical role in the development and maturation of the antibody-producing B lymphocytes (B cells). If a B cell binds weakly to an antigen trapped on the surface of an FDC, it undergoes programmed cell death (apoptosis). On the other hand, a B cell that has a high affinity for the trapped antigen survives to become an antibody-producing plasmablast, and ultimately a memory B cell. This is the fundamental process that underpins the ability of the immune system to respond quickly to attack by pathogenic infection.
But it is not simply a matter of recognition; it appears that a complex interaction of cells and molecules and cellular architecture within the dynamic microenvironment of the lymphoid follicle is required for B cell maturation. The players include connective tissue cells called stromal cells.
“The intrigue of the lymphoid follicle stems from the complexity of its microarchitecture, comprising immune cells and stromal cells, adhesion molecules, cytokines and antigen-antibody complexes, and the relationships between these components, in the formation of B cell-follicular dendritic cell aggregates and the regulation of B cell differentiation,” says Takaya Murakami, the first author of the paper.
Results from a series of experiments both in vitro and in vivo suggest that the splenic cells with the CD35 and B220 proteins on their surface (CD35+B220+ cells) interact with stromal cells to create a niche for migrating B cells, forming cell clusters. The researchers believe that this may play a critical role in FDC network development and the subsequent formation of lymphoid follicles. There is also some evidence that the stromal cells may fuse with the CD35+B220+ cells during this process.
Further investigation of the role of stromal cells in the development of the lymphoid follicles and B cell maturation is planned, says Murakami.
Reference
1. Murakami, T., Chen, X., Hase, K., Sakamoto, A., Nishigaki, C. & Ohno, H. Splenic CD19-CD35+B220+ cells function as an inducer of follicular dendritic cell network formation. Blood 110, 1215–1224 (2007).
