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  • What are the two signals required for T cell-independent activation of B cells?
  • What is the function of a plasma cell?

T cell-dependent activation of b 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, T H 2 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 T H 2 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 ( [link] ).

After initial secretion of IgM, cytokines secreted by T H 2 cells stimulate the plasma cells to switch from IgM production to 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.

1: BCR interaction with antigen on intact pathogen. An antigen on the surface of a bacterium binds to the B cell receptor on the B cell. s: Antigen processing and presentation with MHC II. The antigen is on the MHC II. 3: Antigen presentation and activation of helper T cell. T cell receptor of helper T cell binds to antigen on MHCII. This is stabilized by CD4. Helper T releases cytokines. 4: Cytokines stimulate clonal proliferation and differentiation into memory B cells and antibody-secreting plasma cells.
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.
  • What steps are required for T cell-dependent activation of B cells?
  • What is antibody class switching and why is it important?

Primary and secondary responses

T cell-dependent activation of B cells plays an important role in both the primary and secondary responses associated with adaptive immunity. With the first exposure to a protein antigen, a T cell-dependent primary antibody response occurs. The initial stage of the primary response is a lag period , or latent period , of approximately 10 days, during which no antibody can be detected in serum. This lag period is the time required for all of the steps of the primary response, including naïve mature B cell binding of antigen with BCRs, antigen processing and presentation, helper T cell activation, B cell activation, and clonal proliferation. The end of the lag period is characterized by a rise in IgM levels in the serum, as T H 2 cells stimulate B cell differentiation into plasma cells . IgM levels reach their peak around 14 days after primary antigen exposure; at about this same time, T H 2 stimulates antibody class switching, and IgM levels in serum begin to decline. Meanwhile, levels of IgG increase until they reach a peak about three weeks into the primary response ( [link] ).

During the primary response, some of the cloned B cells are differentiated into memory B cells programmed to respond to subsequent exposures. This secondary response occurs more quickly and forcefully than the primary response. The lag period is decreased to only a few days and the production of IgG is significantly higher than observed for the primary response ( [link] ). In addition, the antibodies produced during the secondary response are more effective and bind with higher affinity to the targeted epitopes. Plasma cells produced during secondary responses live longer than those produced during the primary response, so levels of specific antibody remain elevated for a longer period of time.

A graph with time on the X axis and antibody concentration in serum. At first there is very little antibody (near 0). The lag period does not see a significant increase. In the primary response, IgM peaks for about 5 days and drops. At the same time IgG increases and then drops. This creates an increase in antibody count with a plateau of about 5 days as both antibody types are present. The secondary response sees a peak of IgM for about 1 to 2 days and then a prolonged peak of IgG. The total antibody is also higher but isn’t at its plateau for as long as it is in the primary response.
Compared to the primary response, the secondary antibody response occurs more quickly and produces antibody levels that are higher and more sustained. The secondary response mostly involves IgG.
  • What events occur during the lag period of the primary antibody response?
  • Why do antibody levels remain elevated longer during the secondary antibody response?

Key concepts and summary

  • B lymphocytes or B cells produce antibodies involved in humoral immunity. B cells are produced in the bone marrow, where the initial stages of maturation occur, and travel to the spleen for final steps of maturation into naïve mature B cells.
  • B-cell receptors (BCRs) are membrane-bound monomeric forms of IgD and IgM that bind specific antigen epitopes with their Fab antigen-binding regions. Diversity of antigen binding specificity is created by genetic rearrangement of V, D, and J segments similar to the mechanism used for TCR diversity.
  • Protein antigens are called T-dependent antigens because they can only activate B cells with the cooperation of helper T cells. Other molecule classes do not require T cell cooperation and are called T-independent antigens .
  • T cell-independent activation of B cells involves cross-linkage of BCRs by repetitive nonprotein antigen epitopes. It is characterized by the production of IgM by plasma cells and does not produce memory B cells.
  • T cell-dependent activation of B cells involves processing and presentation of protein antigens to helper T cells, activation of the B cells by cytokines secreted from activated T H 2 cells, and plasma cells that produce different classes of antibodies as a result of class switching . Memory B cells are also produced.
  • Secondary exposures to T-dependent antigens result in a secondary antibody response initiated by memory B cells. The secondary response develops more quickly and produces higher and more sustained levels of antibody with higher affinity for the specific antigen.

Fill in the blank

________ antigens can stimulate B cells to become activated but require cytokine assistance delivered by helper T cells.

T-dependent

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T-independent antigens can stimulate B cells to become activated and secrete antibodies without assistance from helper T cells. These antigens possess ________ antigenic epitopes that cross-link BCRs.

repetitive

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Questions & Answers

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Source:  OpenStax, Microbiology. OpenStax CNX. Nov 01, 2016 Download for free at http://cnx.org/content/col12087/1.4
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