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The dual function of the splenic marginal zone: essential for initiation of anti-TI-2 responses but also vital in the general first-line defense against blood-borne antigens Zandvoort A; Timens WClin Exp Immunol 2002[Oct]; 130 (1): 4-11The splenic marginal zone (S-MZ) is especially well equipped for rapid humoral responses and is unique in its ability to initiate an immune response to encapsulated bacteria (T-cell independent type 2 (TI-2) antigens). Because of the rapid spreading through the blood, infections with blood-borne bacteria form a major health risk. To cope with blood-borne antigens, a system is needed that can respond rapidly to a great diversity of organisms. Because of a number of unique features, S-MZ B cells can respond rapid and efficient to all sorts of blood-borne antigens. These unique features include a low blood flow microenvironment, low threshold for activation, high expression of complement receptor 2 (CR2, CD21) and multireactivity. Because of the unique high expression of CD21 in a low flow compartment, S-MZ B cells can bind and respond to TI-2 antigens even with relatively low-avid B cell receptors. Although TI-2 antigens are in general poorly opsonized by classic opsonins, a particular characteristic of these antigens is their ability to bind very rapidly to complement fragment C3d without the necessity of previous immunoglobulin binding. TI-2 primed S-MZ B cells, already by first passage through the germinal centre, will meet antigen-C3d complexes bound to follicular dendritic cells, allowing unique immediate isotype switching. This explains that the primary humoral response to TI-2 antigens is unique in its characterization by a rapid increase in IgM concurrent with IgG antibody levels.|*Blood-Borne Pathogens[MESH]|Adult[MESH]|Animals[MESH]|Antigen-Antibody Complex/immunology[MESH]|Antigens, CD/immunology[MESH]|Antigens, CD19/immunology[MESH]|Antigens, Differentiation/immunology[MESH]|Antigens, T-Independent/*immunology[MESH]|B-Lymphocyte Subsets/immunology[MESH]|Complement C3d/immunology[MESH]|Disease Susceptibility[MESH]|Humans[MESH]|Immunoglobulin Class Switching[MESH]|Immunoglobulin M/biosynthesis[MESH]|Immunologic Memory/immunology[MESH]|Infant[MESH]|Lymphocyte Activation[MESH]|Macromolecular Substances[MESH]|Membrane Proteins/immunology[MESH]|Mice[MESH]|Mice, Mutant Strains[MESH]|Mice, Nude[MESH]|Receptors, Complement 3d/immunology[MESH]|Spleen/blood supply/*immunology/microbiology/ultrastructure[MESH]|Splenectomy/adverse effects[MESH]|Tetraspanin 28[MESH] |
