At the end of this section, you can:
- Describe the production and maturation of B cells.
- Compare the structure of B cell receptors and T cell receptors
- Compare T-dependent and T-independent B cell activation
- Compare primary and secondary antibody responses
Humoral immunity refers to the adaptive immune defense mechanisms mediated by antibodies secreted by B lymphocytes or B cells. This section focuses on B cells and discusses their production and maturation, receptors, and activation mechanisms.
B cell production and maturation
B cells, like T cells, are formed from multipotent cells.hematopoietic stem cells(HSC) in the bone marrow and follow a pathway through lymphoid stem cells and lymphoblasts (cf.Figure 17.12). Unlike T cells, however, lymphoblasts destined to become B cells leave thebone marrowand migrate to the thymus for maturation. Instead, any B cells in the bone marrow continue to mature.
The first step in B cell maturation is an assessment of the functionality of their antigen-binding receptors. happens throughpositive choicefor B cells with normally functioning receptors. a mechanism ofnegative selectionthen used for removalautoreactive B cellsand minimize the riskautoimmunity. Negative selection of self-responsive B cells may involve removal byApoptosisB. Edit or modify the receptors so that they are no longer autoreactive or inducersanergiain the B cell. Immature B cells that undergo selection in the bone marrow and then migrate to thebasisto its final stage of maturity. there they goNaive mature B cells, that is, mature B cells that have not yet been activated.
check your understanding
- Compare B cell maturation with T cell maturation.
B cell receptors
Like T cells, B cells have antigen-specific receptors with different specificities. Although they are dependent on T cells for their optimal function, B cells can activate without the help of T cells.B cell receptors (BCRs)for naive mature B cells are membrane-bound monomeric forms ofIgDmiIgM. you have two alikeheavy chainsand two equallight chainsconnected by disulfide bonds in a basic "Y" shape (Figure 18.20). The Y-shaped rod of the molecule, the constant region of the two heavy chains, spans the B cell membrane.antigen binding sitesexposed to the outside of the B cell are involved in the binding of pathogen-specific epitopes to initiate the activation process. It is estimated that each naive mature B cell has more than 100,000 BCRs on its membrane, and each of these BCRs has identical epitope-binding specificity.
To be prepared to respond to a wide range of microbial epitopes, B cells are used, like T cells.genetic rearrangementhundreds of gene segments to provide the necessary diversity of receptor specificities. The variable region ofBCRheavy chain consists ofSegmentos V, D and J, similar to the β chain of the TCR. The variable region of the BCR light chain consists of segments V and J, similar to the α chain of the TCR. The genetic rearrangement of all possible combinations of V-J-D (heavy chain) and V-J (light chain) provides millions of unique antigen-binding sites for the BCR and for antibodies secreted upon activation.
An important difference between BCRs and TCRs is the way in which they can interact with antigenic epitopes. While TCRs can only interact with antigenic epitopes presented within the antigen-binding cleft ofMHC IoMHCII, BCRs do not require antigen presentation with MHC; can interact with or with epitopes on free antigensepitopedisplayed on the surface of intact pathogens. Another important difference is that TCRs only recognize protein epitopes, whereas BCRs can recognize epitopes associated with different classes of molecules (eg, proteins, polysaccharides, lipopolysaccharides).
Activation of B cells occurs by different mechanisms, depending on the molecular class of the antigen. Activation of a B cell by a protein antigen requires the B cell to act as an APC and present the protein epitopes to MHC II helper T cells. Due to its dependence on T cells zB cell activation, Protein antigens are classified asT-dependent antigens. In contrast, polysaccharides, lipopolysaccharides, and other non-protein antigens are consideredT-independent antigensbecause they can activate B cells without antigen processing and presentation to T cells.
Figure18h20 B cell receptors are embedded in B cell membranes. Variable regions of all receptors on a single cell bind to the same specific antigen.
check your understanding
- What types of molecules serve as BCRs?
- What are the differences between TCRs and BCRs in terms of antigen recognition?
- Which classes of molecules are T-dependent antigens and which are T-independent antigens?
Independent activation of T cells from B cells
Activation of B cells without the involvement of helper T cells is calledIndependent activation of T cellsand occurs when BCRs interact with T-independent antigens. They have T-independent antigens (eg, polysaccharide capsules, lipopolysaccharides).repeating epitope unitswithin its structure, and this repetition makes possible theredof multiple BCRs that provide the initial signal for activation (Figure 18.21). Since T cells are not involved, the second signal must come from other sources, such as B.toll receptorscomTYCOONor interactions with factors of thecomplementary system.
Once a B cell is activated, it learnsclonal propagationand the daughter cells differentiate into plasma cells.plasma cellsthey are antibody factories that secrete large amounts of antibodies. After differentiation, the surface BCRs disappear and the plasma cells secretePentameros IgMMolecules that have the same antigenic specificity as BCRs (Figure 18.21).
The T cell-independent response is short-lived and does not result in the production ofmemory B cells. Therefore, it will not result in a secondary response to subsequent exposures to T.
Figure18.21 T-independent antigens have repetitive epitopes that can induce B cell recognition and activation without T cell involvement. B cells. Upon activation, B cells proliferate and differentiate into antibody-secreting plasma cells.
check your understanding
- What two signals are required for independent activation of T cells from B cells?
- What is the function of a plasma cell?
T cell dependent B cell activation
T cell-dependent activation of B cells is more complex than T cell-independent activation, but the resulting immune response is stronger and memory develops. T cell dependent activation can occur in response tofree protein antigensor to protein antigens associated with an intact pathogen. Stimulating the interaction between the BCRs in a mature naïve B cell and a free protein antigeninternalizationantigen, while interaction with antigens associated with an intact pathogen initiates the extraction of antigen from the pathogen prior to internalization. Once internalized in the B cell, the protein antigen is processed and presentedMHCII. The presented antigen is then recognized byhelper T lymphocytesspecific for the same antigen. Helper T-cell TCR recognizes foreign and T-cell antigensCD4The molecule interacts with MHC II on the B cell. The coordination between B cells and helper T cells specific for the same antigen is denoted asassociated recognition.
Once activated by linked detection,TH2 cellsproduce and separatecytokinesthat activate the B cell and cause proliferation in clonal daughter cells. After several cycles of proliferation, additional cytokines produced by TH2 cells stimulate differentiation of activated B cell clones inmemory B cells, which respond rapidly to subsequent exposures to the same protein epitope, and plasma cells lose their membrane BCRs and initially pentameric IgM (Figure 18.22).
After the initial secretion of IgM,cytokinesbeyond the tH2 cells stimulate plasma cells to switch from producing IgM to producingIgG,IgA, oIgE. This process, calledclass changeoIsotypenwechsel, permittedplasma cellscloned from the same activated B cell to produce a variety of antibody classes with the same epitope specificity. Class change is done bygenetic rearrangementof gene segments that encodeconstant area, which determines the class of an antibody. EITHERvariable regionit is not altered such that the new class of antibody retains the specificity of the original epitope.
Figure18.22 In T cell-dependent B cell activation, the B cell recognizes and internalizes an antigen and presents it to an antigen-specific helper T cell. The helper T cell interacts with the antigen presented by the B cell, which activates the T cell and stimulates the release of cytokines, which then activate the B cell. B cell activation triggers proliferation and differentiation into B cells and plasma cells .
check your understanding
- What steps are required for T cell-dependent activation of B cells?
- What is an antibody class switch and why is it important?
Primary and secondary reactions
T cell-dependent activation of B cells plays an important role in the primary and secondary responses associated with adaptive immunity. When first exposed to a protein antigen, it becomes dependent on T cells.primary antibody responseoccurs. The initial stage of the primary reaction is adelay time, olatency, about 10 days, during which no antibodies are detected in the serum. This lag time is the time required for all steps of the primary response, including binding of antigen-free mature B cells to BCRs, antigen processing and presentation, helper T cell activation, B cell activation, and clonal proliferation. The end of the latency period is marked by an increase in serum IgM levels, asTH2 cellsStimulate B cell differentiationplasma cells.IgMlevels peak approximately 14 days after exposure to the primary antigen; almost at the same time,H2 stimulates antibody class switching and serum IgM levels begin to fall. Meanwhile, IgG levels rise to peak about three weeks after the primary response (Figure 18.23).
During the primary response, some of the cloned B cells differentiatememory B cellsscheduled to respond to subsequent exposures. EITHERside reactionoccurs faster and stronger than the primary reaction. The time span is reduced to a few days and IgG production is significantly greater than that seen in the primary response (Figure 18.23). Furthermore, the antibodies produced during the secondary reaction are more effective and bind to the target epitopes with higher affinity. Plasma cells produced during secondary reactions live longer than those produced during the primary reaction, so specific antibody levels remain elevated for a longer period of time.
Figure18.23 Compared to the primary response, the secondary antibody response occurs more rapidly and results in higher and more persistent antibody levels. The secondary reaction mainly affects IgG.
check your understanding
- What events occur during the latent period of the primary antibody response?
- Why do antibody levels stay elevated longer during the secondary antibody response?