Antigens: Thymus‐dependent

Abstract

B cells secrete antibodies that mediate protection against a great variety of pathogens. There are two classes of antigens for B cells, T cell‐dependent (thymus‐dependent, TD) and T cell‐independent (TI) antigens. The former require the presence of cognate T‐helper (TH) cells to trigger a B‐cell response, whereas the TI antigens can mount an antibody response in the absence of TH. A large class of antigens, namely proteins on pathogen surfaces, are both TI and TD: They are able to induce a TI IgM (immunoglobulin M) antibody response, since they are highly repetitive and linked to toll‐like receptor (TLR) ligands and they induce a TD response, since they are proteins. Epitope repetitiveness, presence of TLR‐ligands and T help together shape the quantity, quality and duration of an antibody response.

Key Concepts:

  • TI antigens induce antibody responses in the absence of TH.

  • TI antibody responses are mostly of the IgM isotype and short‐lived.

  • TD antigens require TH cells to induce an antibody responses.

  • TD antibody responses are usually of the IgG isotype and more long‐lived.

  • Pathogens are complex antigens and are both TI (they are repetitive and contain TLR ligands) and TD (they contain proteins and induce TH).

  • This combination of TI and TD makes pathogens such strong immunogens for B cells.

  • Antigen‐repetitiveness and presence of TLR ligands modulate the overall magnitude of the antibody responses.

  • Presence of TH imprints memory into the antibody responses by allowing the formation of long‐lived plasma cells as well as memory B cells.

Keywords: antibody; vaccine; T/B collaboration; toll‐like receptor ligands

Figure 1.

Three steps of T cell–antigen‐presenting cell (APC) interaction. (a) T cells are stimulated by MHC–peptide complexes on APCs via their T‐cell receptor (TCR). (b) This induces the upregulated expression of CD40 ligand (CD40L) and TRANCE (RANK ligand), which triggers CD40 and RANK, respectively, on APCs. (c) On activation, APCs increase expression of costimulatory molecules, such as B7 family members and cytokines, such as IL‐12, leading to further activation of T cells.

Figure 2.

B‐cell activation (− to +++) is governed by antigen order and repetitiveness.

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Further Reading

Dörner T and Radbruch A (2008) Antibodies and B cell memory in viral immunity. Immunity 27(3): 384–392.

Hinton HJ, Jegerlehner A and Bachmann MF (2008) Pattern recognition by B cells: the role of antigen repetitiveness versus toll‐like receptors. Current Topics in Microbiology and Immunology 319: 1–15.

Jennings GT and Bachmann MF (2008) The coming of age of virus‐like particle vaccines. Biological Chemistry 389(5): 521–536.

Lanzavecchia A and Sallusto F (2007) Toll‐like receptors and innate immunity in B‐cell activation and antibody responses. Current Opinion in Immunology 19: 268–274.

Wrammert J and Ahmed R (2008) Maintenance of serological memory. Biological Chemistry 389(5): 537–539.

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Bachmann, Martin F(Sep 2009) Antigens: Thymus‐dependent. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000502.pub2]