Antigens: Thymus Independent

Goran Möller, Stockholm University, Stockholm, Sweden

Published online: April 2001

DOI: 10.1038/npg.els.0000504

Full Article on Wiley Online Library

Thymus-independent (TI) antigens are capable of directly activating B lymphocytes into antibody production without helper cells or helper factors. These antigens are mostly of microbial origin, such as lipopolysaccharide from Gram-negative bacteria, polymerized flagellin, pneumococcal polysaccharide type III, and levans and dextrans from bacteria and they normally induce an early specific immunoglobulin M antibody response, which often exhibit cyclical fluctuations. Apart from their ability to induce an immune response without T helper lymphocytes and their microbial origin, there is little in common between different TI antigens.

Keywords: B lymphocytes; T lymphocytes; immunological tolerance; antibody synthesis; polyclonal B cell activation; B cell antigen receptors; toll genes; B cell activation receptors; B cell subpopulations

	Figure 1. Typical cyclical appearance of immunoglobulin (Ig) M antibody-producing cells in the response to either lipopolysaccharide (LPS) (thymus independent (TI) type I) or dextran (TI type II) after in vivo immunization. If a switch to IgG3 antibodies occurs, the second peak will not appear.
	Figure 2. B cells possess immunoglobulin receptors and activation receptors, similar to pattern-recognizing receptors (PRRs), which initiate defence against microorganisms in insects and mammals. A polyclonal B-cell activator possesses activating structures analogous to pathogen-associated molecular patterns (PAMPs) in various microorganisms. The PRRs bind PAMPs with low affinity, but a sufficient concentration of PAMPs will activate B lymphocytes into antibody synthesis. As a very large fraction (about 30%) of B cells possesses PRRs for lipopolysaccharide (LPS), there will be induction of antibodies of nearly all specificities (a polyclonal antibody response).
	Figure 3. B cells are activated by polyclonal B-cell activators (PBAs), which do not interact with the BCRs (a). However, if the Ig receptors recognize antigenic determinants on the PBA, they will bind them with very high affinity. In this way a low concentration of a PBA can activate specific cells into specific antibody synthesis, although activation is (immunologically) nonspecifically delivered to pattern-recognizing receptors (PRRs) from pathogen-associated molecular patterns (PAMPs) on the PBA (b). LPS, lipopolysaccharide.
	Figure 4. A B-cell subpopulation has the same activation receptor (pattern-recognizing receptor; PRR) but different immunoglobulin (Ig) receptors. A subpopulation can be up to 30% of all B cells. A B-cell clone has identical Ig receptors, but different activation receptors. A clone is about 0.001–0.0001% of all B cells.
	Figure 5. Tolerance to the thymus-independent (TI) antigen dextran. Mice were left untreated or made tolerant to 10 mg dextran. After 4 days half of the mice were treated with dextranase (D:ase) to remove dextran and thereafter immunized with dextran itself (left) or a thymus-dependent (TD) dextran conjugate (right). Although the mice remained tolerant of dextran, they produced a normal antidextran immune response to the TD dextran–protein conjugate.
	Figure 6. Explanation at the cellular level of experiments shown in Figure 5. Two cells belonging to the same antidextran-specific clone are shown. In (a) the cells can bind dextran with its immunoglobulin (Ig) receptor and can react to the pathogen-associated molecular pattern (PAMP) of dextran with its pattern-recognizing receptor (PRR). As a very high dose of dextran was given, these cells will become tolerant and probably die. In (b) the cells also bind dextran with its Ig receptor, but remain unaffected because they possess PRRs that do not recognize dextran. When dextran has been removed by dextranase treatment, the cell can be activated by T helper cells, which secrete or possess PAMPs activating a corresponding PRR on the B cell. TI, thymus independent; TD, thymus dependent.
	Figure 7. B lymphocytes in normal mice express both activation (pattern-recognizing receptor; PRR) and immunoglobulin (Ig) receptors. However, in lipopolysaccharide (LPS) mutant mice the activation receptor is not expressed (in C57BL/10ScCr mice), as shown in the figure, or else a defective product of the Lps (Tlr4) gene is expressed (in C3H/HeJ mice). T_H, T helper cell.

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Further Reading
	Boman HG (1998) Gene-encoded peptide antibiotics and the concept of innate immunity: an update review. Scandinavian Journal of Immunology 48: 15–25.
	Carrol MC and Janeway CA (1999) Innate immunity. Current Opinion in Immunology 11: 1–12.
	Coutinho A and Möller G (1974) Immune activation of B cells: evidence for ‘one non-specific triggering signal’ not delivered by the Ig receptors. Scandinavian Journal of Immunology 3: 133–146.
	Kopp EB and Medzhitov R (1999) The Toll family and control of innate immunity. Current Opinion in Immunology 11: 13–18.
	Ulevitch RJ and Tobias PS (1999) Recognition of Gram-negative bacteria and endotoxin by the innate immune system. Current Opinion in Immunology 11: 19–27.

Article Title:	Antigens: Thymus Independent
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