T Dependent Antigen and T Independent Antigen

Activation of B cells requires two signals. Depending on the nature of the antigen, B-cell activation proceeds by two different routes, one dependent on helper T cells (TH cells), the other not.  In the case of T dependent antigen the interaction between CD40 of B Cells and CD40 ligand of T cells gives second signal but in T independent antigen, cross-linking of membrane bound immunoglobulin to polymeric carbohydrate gives the needed signal.

B cells activation by T-independent antigen and T-dependent antigen
(Source: Kuby Immunology)

The B-cell response to thymus-dependent (TD) antigens requires direct contact with TH cells, not simply exposure to TH-derived cytokines.

 Antigens that can activate B cells in the absence of this kind of direct participation by TH cells are known as thymus-independent (TI) antigens. TI antigens are divided into types 1 and 2, and they activate B cells by different mechanisms whereas polymeric proteins e.g., bacterial flagellin acts as Type 2 thymus-independent (TI-2) antigens.

T Independent (TI) Antigen

A typical large polysaccharide is made up of repeating sequences of few simple sugars so it has multiple copies of identical antigenic determinants.

When a specific naïve B cells come in contact with such antigens, these antigenic determinants bind the surface IgM and IgD receptors. This binding leads to clustering of surface immunoglobulins which generates a signal, strong enough to activate the naïve B cells.   This activated B cells produces and releases first immunoglobulin i.e. IgM.

Most TI-1 antigens are polyclonal B-cell activators (mitogens); i.e. they are able to activate B cells regardless of their antigenic specificity.  At higher concentrations, some TI-1 antigens will stimulate proliferation and antibody secretion by as many as one third of all B cells but in lower concentrations of TI-1 antigens, only those B cells specific for epitopes of the antigen will be activated.

TI-2 antigens activate B cells by extensive crosslinking of membrane bound immunoglobulin (mIg) receptor. 

Unlike TI-1 antigens, TI-2 antigens do not act as polyclonal activator, activate only mature B cells and may require cytokines derived from TH cells.

Interaction of B cell receptors with T independent antigen

Main features of T Independent Antigen (Ti-Ag)

  • Antigens that stimulate B-cells directly, without co-stimulation by helper T-cells
  • Usually polysaccharides or lipopolysaccharides (e.g. bacterial capsules)
  • Cross link antigen receptors on the surface of B-cells to activate them
  • Don’t generate strong immune response (no memory cells, IgM is the only antibody class produced, and the immunity doesn’t last long).

T Dependent Antigen (Td-Ag)

Humoral response to protein and most other antigens requires interaction of B cells with helper T cells. These are thymus-dependent or simply T-dependent (TD) responses. B cell activation by T dependent antigens require contact dependent help delivered by the interaction between CD40 on B cells and CD40L on activated  TH cells.

Main steps during B-cell activation by a thymus-dependent antigen:

  • Soluble protein antigens which bind to membrane bound immunoglobulin on the surface of B Cell are internalized, processed and are displayed as peptide-MHC-II complexes.
  • TH  cell recognizes class II MHC-antigen complex on B-cell surface via TCR. It also interacts with costimulatory molecule B7 via CD28. These interactions activates TH cell. Activated TH  cells produces various cytokines.
  • TH cell begins to express CD40L and interacts with CD40 of the B Cell. The interaction between CD40 and CD40L provides second signal to activate B cell.
  • B cells begins to express receptors for various cytokines and binds to cytokines released from TH cells. Which activates B cell and differentiates them to plasma cells.
  • The activated B-cell clonally proliferates to produce a population of plasma cells and memory cells, which all recognize the same antigen

This CD40/CD40L interaction is essential for B-cell survival, the formation of germinal centers, the generation of memory-cell populations and somatic hypermutation (for affinity maturation).

Difference between T dependent Antigen and T independent Antigen

T dependent (TD) Antigen
T independent Antigen
Soluble proteins 
Bacterial cell wall components Lipopolysaccharide (LPS), Capsular polysaccharide, flagella etc.

Antigen is processed and displayed in the surface of Antigen Presenting Cells (B Cells) in association with MHC-II.

Antigen processing is not needed

Immunogenic over wide range of dose

Dose dependent immunogenicity
No polyclonal activation i.e. Activate B cells monoclonally
Polyclonal activation of B cells occur in high doses of Type-I TI Antigens
Immunologic memory present
No Immunologic Memory
Affinity Maturation- YesAffinity Maturation- No
Isotype Switching occurs  (i.e. antibodies of all classes are produced)No Isotype switching 
( Antibody response is restricted to IgM and IgG3)
Activate mature B cells only
Activate both mature and immature B cells

References and further reading:

  • Cellular and Molecular Immunology, 9th Edition
  • Kuby Immunology, 7th Edition
  • Roitt’s Essential Immunology, 13th Edition
About tankeshwar 367 Articles
Hello, thank you for visiting my blog. I am Tankeshwar Acharya. Blogging is my passion, I am working as a Asst. Professor and Microbiologist at Department of Microbiology and Immunology, Patan Academy of Health Sciences, Nepal. If you want me to write about any posts that you found confusing/difficult, please mention in the comments below.

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