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

Clin Exp Immunol. 2002 Oct;130(1):4-11. doi: 10.1046/j.1365-2249.2002.01953.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Animals
  • Antigen-Antibody Complex / immunology
  • Antigens, CD / immunology
  • Antigens, CD19 / immunology
  • Antigens, Differentiation / immunology
  • Antigens, T-Independent / immunology*
  • B-Lymphocyte Subsets / immunology
  • Blood-Borne Pathogens*
  • Complement C3d / immunology
  • Disease Susceptibility
  • Humans
  • Immunoglobulin Class Switching
  • Immunoglobulin M / biosynthesis
  • Immunologic Memory / immunology
  • Infant
  • Lymphocyte Activation
  • Macromolecular Substances
  • Membrane Proteins / immunology
  • Mice
  • Mice, Mutant Strains
  • Mice, Nude
  • Receptors, Complement 3d / immunology
  • Spleen / blood supply
  • Spleen / immunology*
  • Spleen / microbiology
  • Spleen / ultrastructure
  • Splenectomy / adverse effects
  • Tetraspanin 28


  • Antigen-Antibody Complex
  • Antigens, CD
  • Antigens, CD19
  • Antigens, Differentiation
  • Antigens, T-Independent
  • CD81 protein, human
  • Cd81 protein, mouse
  • Immunoglobulin M
  • Macromolecular Substances
  • Membrane Proteins
  • Receptors, Complement 3d
  • Tetraspanin 28
  • leu-13 antigen
  • Complement C3d