title: 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.
abstract: The 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University Hospital Groningen, Groningen, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Zandvoort
authors.forename: W
authors.initials: W
authors.lastname: Timens
mesh_terms: D000328:Adult; D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D018941:Antigens, CD19 / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology; D000955:Antigens, T-Independent / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology; D017848:Blood-Borne Pathogens; D015933:Complement C3d / Q000276:immunology; D004198:Disease Susceptibility; D006801:Humans; D017578:Immunoglobulin Class Switching; D007075:Immunoglobulin M / Q000096:biosynthesis; D007156:Immunologic Memory / Q000276:immunology; D007223:Infant; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D008819:Mice, Nude; D017464:Receptors, Complement 3d / Q000276:immunology; D013154:Spleen / Q000098:blood supply / Q000276:immunology* / Q000382:microbiology / Q000648:ultrastructure; D013156:Splenectomy / Q000009:adverse effects; D060225:Tetraspanin 28
chemical_list: D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D018941:Antigens, CD19; D000943:Antigens, Differentiation; D000955:Antigens, T-Independent; C554798:CD81 protein, human; C554799:Cd81 protein, mouse; D007075:Immunoglobulin M; D046911:Macromolecular Substances; D008565:Membrane Proteins; D017464:Receptors, Complement 3d; D060225:Tetraspanin 28; C062010:leu-13 antigen; D015933:Complement C3d