Question

Subject: intro to immunology

Question: Explain the difference between T-Independent and T-Dependent B-cell responses, describing the B-cell subsets that participate in each type of response and the biochemical nature of the antigens that evoke them.

Answer 1

1.T Cell-Independent Activation of B cells:-

Activation of B cells without the cooperation of helper T cells is referred to as T cell-independent activation and occurs when BCRs interact with T-independent antigens. T-independent antigens (e.g., polysaccharide capsules, lipopolysaccharide) have repetitive epitope units within their structure, and this repetition allows for the cross-linkage of multiple BCRs, providing the first signal for activation (Figure 1). Because T cells are not involved, the second signal has to come from other sources, such as interactions of toll-like receptors with PAMPs or interactions with factors from the complement system.

Once a B cell is activated, it undergoes clonal proliferation and daughter cells differentiate into plasma cells. Plasma cells are antibody factories that secrete large quantities of antibodies. After differentiation, the surface BCRs disappear and the plasma cell secretes pentameric IgM molecules that have the same antigen specificity as the BCRs (Figure 1).

The T cell-independent response is short-lived and does not result in the production of memory B cells. Thus it will not result in a secondary response to subsequent exposures to T-independent antigens.

Figure 1. T-independent antigens have repeating epitopes that can induce B cell recognition and activation without involvement from T cells. A second signal, such as the interaction of TLRs with PAMPs (not shown), is also required for activation of the B cell. Once activated, the B cell proliferates and differentiates into antibody-secreting plasma cells.

T Cell-Dependent Activation of B cells:-

Figure 2. Click for a larger image. In T cell-dependent activation of B cells, the B cell recognizes and internalizes an antigen and presents it to a helper T cell that is specific to the same antigen. The helper T cell interacts with the antigen presented by the B cell, which activates the T cell and stimulates the release of cytokines that then activate the B cell. Activation of the B cell triggers proliferation and differentiation into B cells and plasma cells.

T cell-dependent activation of B cells is more complex than T cell-independent activation, but the resulting immune response is stronger and develops memory. T cell-dependent activation can occur either in response to free protein antigens or to protein antigens associated with an intact pathogen. Interaction between the BCRs on a naïve mature B cell and a free protein antigen stimulate internalization of the antigen, whereas interaction with antigens associated with an intact pathogen initiates the extraction of the antigen from the pathogen before internalization. Once internalized inside the B cell, the protein antigen is processed and presented with MHC II. The presented antigen is then recognized by helper T cells specific to the same antigen. The TCR of the helper T cell recognizes the foreign antigen, and the T cell’s CD4 molecule interacts with MHC II on the B cell. The coordination between B cells and helper T cells that are specific to the same antigen is referred to as linked recognition.

Once activated by linked recognition, TH2 cells produce and secrete cytokines that activate the B cell and cause proliferation into clonal daughter cells. After several rounds of proliferation, additional cytokines provided by the TH2 cells stimulate the differentiation of activated B cell clones into memory B cells, which will quickly respond to subsequent exposures to the same protein epitope, and plasma cells that lose their membrane BCRs and initially secrete pentameric IgM (Figure 2).

After the initial secretion of IgM, cytokines secreted by TH2 cells stimulate the plasma cells to switch from IgM production to the production of IgG, IgA, or IgE. This process, called class switching or isotype switching, allows plasma cells cloned from the same activated B cell to produce a variety of antibody classes with the same epitope specificity. Class switching is accomplished by genetic rearrangement of gene segments encoding the constant region, which determines an antibody’s class. The variable region is not changed, so the new class of antibody retains the original epitope specificity.

dependent (TD) Antigen	T independent Antigen
Soluble proteins	Bacterial cell wall components Lipopolysaccharide (LPS), Capsular polysaccharide, flagella, etc.
The antigen is processed and displayed on the surface of Antigen Presenting Cells (B Cells) in association with MHC-II.	Antigen processing is not needed
Immunogenic over a wide range of doses.	Dose-dependent immunogenicity
No polyclonal activation i.e. Activate B cells monoclonal	Polyclonal activation of B cells occurs in high doses of Type-I TI Antigens
Immunologic memory present	No Immunologic Memory
Affinity Maturation- Yes	Affinity 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