B Cell Activation And Antibody Production Ppt
B Cell Activation. Ab Responses to most Ags require thymus (TD). Ag must be a protein. Humoral response leads to: Affinity maturation. . T-cell dependent antigens T-cell independent antigens T cell dependent B cell antigens Majority of antigens. Most protein antigens. T cell help required for B cell activation and antibody production. T cell independent Do not require thymus. Location of B Cell Activation Antigen activated B cells remain in T cell zones of LN.
Overview
B cells are lymphocytes which, along with T cells, constitute the adaptive immune system, providing a specifically targeted response to infection. For detailed information on B cell function, activation and lineage, refer to our B cell mini-review.
B cell markers
Selecting the right marker to identify B cell subtypes can be a time consuming process. In the tables below we have listed general key markers expressed by B cells and also markers that can be used to identify peripheral B cell subtypes.
Further resources have been developed to aid B cell marker selection:
- A flow cytometry guide to B cell immunophenotyping
- Interactive online marker database enabling the identification of B cell markers; providing information about these markers, where they are expressed and available antibodies
- Mini-review of B cells lineage, function and activation including detailed information on B cell markers
- Marker expression and lineage posters for human and mouse which include data on B cells
- Detailed overview of specific antibodies for CD20, CD19 and B220 (CD45R) for human and mouse
Table 1. Cell surface CD markers expressed by B cells
Name | Function | B Cell Subtype Expression |
|---|---|---|
Regulates intracellular B cell signaling by amplifying Src-family kinase activity | Expressed on all B-lineage cells; Pan B cell marker | |
Functions as a membrane embedded Ca2+ channel | Mature B cells | |
C3d and Epstein-Barr virus receptor that interacts with CD19 to induce B cell inflammatory responses | Mature B cells | |
Functions as a mammalian lectin for α2,6-linked sialic acid that regulated follicular B cell survival | Mature B cells | |
Low affinity IgE receptor that influences IgE production | Activated B cells | |
Function is still unknown | Expressed on all B-lineage cells; Pan B cell marker | |
Critical survival factor for GC B cells; ligand for CD154 expressed by T cells | B cells | |
Negative regulator of signal transduction; B cell ligand for CD100 (Semaphorin 3D) | Expressed on all B-lineage cells; Pan B cell marker | |
Contain highly conserved motifs in their cytoplasmic domains for tyrosine phosphorylation and Src family kinase docking to initiate B cell activation | Surface Ig+ B cells | |
Binds to extracellular matrix compartments | Plasma cells |
Adapted from LeBien and Tedder 2008. Ig, immunoglobulin; GC, germinal center
Table 2. Characterization of peripheral B cell subsets in human and mouse
B Cell Subset | Human Phenotype | Mouse Phenotype |
|---|---|---|
Transitional | CD20+CD27- CD38hi IgM+CD24hi BR3+ | B220(CD45R)+ CD93+CD24hi IgM+ BR3+ TACI+ |
Follicular | IgMlo CD23+CD93- CD19+CD20+CD21+ CD22+ | IgMloB220(CD45R)hi CD38+ CD23+ CD22+ CD19+ |
Marginal zone | IgMhiIgDlo CD1c+ CD24+ CD19+ CD20+ CD21+ | IgMhiIgDlo CD1d+CD9+ CD21+CD22+ CD35+ B220(CD45R)+ CD23+ |
Germinal center | CD20+CD38+ BR3+ IgD- | B220(CD45R)+ GL7+CD95+ PNA+ BR3+ IgD-IgM- |
Plasma cells | CD20- CD38hiCD27hi CD138+ TACI+ and/or BCMA+ CD126+ CD319+ CD78+ | IgD-B220(CD45R)lo CD138hi TACI+ and/or BCMA+ CD126+CD184+ CD320+ Gokulamlo Seetha Telugu Movie: Check out the latest news about Pawan Kalyan's Gokulamlo Seetha movie, story, cast & crew, release date, photos, review, box office collections and much more only on. Credited cast: Pawan Kalyan. Sirisha Srinivasa Rao Kota. Muddukrishnayya Harish. Bhaskar Sudhakar. Baburao Srihari. Hari Rest of cast listed alphabetically: Achyuth. |
Memory B Cell | CD20+CD38-CD27+ CD80+ CD84+ CD86+ | B220(CD45R)+ CD80+ CD73+ CD273+ CD38+ CD84+ CD86+ |
Adapted from Naradikian et al. 2014 and Melchers 2015. BCMA, B cell maturation antigen; BR3, B lymphocyte stimulator receptor 3; TACI, transmembrane activator and cyclophilin ligand interactor
B cell lineage
B cells are derived from the bone marrow (or bursa cells in birds), originating from hematopoietic stem cells, which differentiate into multipotent progenitor cells then into common lymphoid progenitor cells. The subsequent developmental process of B cells is complex with many different stages, which is dependent upon the stimuli received and through which the B cell gains its antigen specificity. At these stages of development different surface antigens are expressed enabling detection of specific B cells during their maturation process. Figure 1 below show the B cell lineage of both humans and mice alongside key markers for the different stages of development. For further information on B cell development, refer to our B cell mini-review.
(b)
Mouse B cell lineage
Figure 1: Human (a) and mouse (b) B cell lineage. Click on the B cell lineage relevant image above to obtain human and mouse specific posters and guides.
B cell function and activation
B cell activation begins by the recognition and binding of an antigen by the B cell receptor. This can either take place in a T cell dependent or T cell independent manner. Once the antigen has bound to the B cell, receptor mediated endocytosis takes place engulfing the antigen into the B cell, where the antigen is then degraded. These degraded antigen fragments are then presented on the surface of the B cell in complex with MHC class II molecules to T cells.
T helper cells which have been activated by the same antigen recognize these antigen fragments and bind to the antigen-MHC class II complexes via their T cell receptor. This binding stimulates B cell proliferation and promotes differentiation into plasma cells, which switch from generating B cell receptors, which are membrane bound, to secreted ones called antibodies.
Further stimulation of this process by T cells occurs via expression of CD40L which binds to CD40 expressed on the B cell and by the release of cytokines such as IL-4 and IL-21. In T cell independent activation of B cells, stimulation is by the binding of the pathogen to toll-like receptors and/or by the cross linking of B cell receptors to repeated epitopes on the pathogen.
The T cell dependent activation of B cells is a longer process than T cell independent activation, taking several days, however higher affinity antibodies are produced providing a much more specific response to infection.
The differentiation of activated B cells is a two-step process. Firstly plasmablasts develop forming short lived plasma cells followed by the development of longer lived plasma cells and memory B cells for life long protection. The second stage of development takes place in germinal centres which form inside lymphoid follicles, facilitated by T follicular helper cells.
Future infections by the same pathogen will activate the memory B cells, developed during the initial infection by the pathogen by the process described above. Here again the antigen is recognized, bound and internalized by receptor mediated endocytosis, which as before can be T cell dependent or independent. The fragmented pathogen antigens are presented to T cells in complex with MHC class II molecules. Following T cell receptors binding of this complex the memory B cells are stimulated into plasmablasts or plasma cells generating more plasma cells and memory B cells. This process of memory B cell activation is much quicker in generating a specific response to the infecting pathogen. For further information on B cell function and activation refer to our B cell mini-review.
Last Updated on: by
B lymphocytes, the cells that produce antibodies, were so called because in birds they were found to mature in an organ called the Bursa of Fabricius. In mammals, no anatomic equivalent of the bursa exists, and the early stages of B cell maturation occur in the bone marrow. Thus, B lymphocytes now refer to bone marrow–derived lymphocytes.
B cells are found in the germinal centers of the lymph nodes, in the white pulp of the spleen, and in the MALT. B cells perform two important functions:
- They differentiate into plasma cells and produce antibodies.
- They can present antigen to helper T cells (Act as Antigen Presenting Cells).
The major subsets of B cells are follicular B cells, marginal zone B cells, and B-1 cells, each of which is found in distinct anatomic locations within lymphoid tissues. Follicular B cells express highly diverse, clonally distributed sets of antibodies that serve as cell surface antigen receptors and as the key secreted effector molecules of adaptive humoral immunity. In contrast, B-1 and marginal-zone B cells produce antibodies with very limited diversity.
Origin of B cells
B-cell development begins in the bone marrow with the asymmetric division of an HSC and continues through a series of progressively more differentiated progenitor stages to the production of common lymphoid progenitors(CLPs), which can give rise to either B cells or T cells. Progenitor cells that remain in the bone marrow become B cells. B cell precursors, during embryogenesis, first proliferate and develop in the fetal liver. From there, they migrate to the bone marrow, the main site of B-cell maturation in the adults. The Pre-B cells have only µ heavy chains in the cytoplasm but do not have surface immunoglobulin and light chains. Pre-B cells are found in the bone marrow, while mature B cells are found in the circulation.
According to clonal selection theory, each immunologically competent B cell possesses receptor for either IgM or IgD that can combine with one antigen or closely related antigens. After binding of the antigen, the B cell is activated to proliferate and form a clone of cells. Selected B cells are transformed to plasma cells that secrete antibodies specific for the antigen. Plasma cells synthesize the immunoglobulin with the same antigenic specificity as those carried by activated B cells.
B cells mature in two phases:
- Antigen-independent phase, which consists of stem cells and pre-B cells
- Antigen-dependent phase, which consists of the cells, such as activated B cells and plasma cells that proliferate on interactions of antigen with B cells.
B cells possess surface IgM, which acts as a receptor for antigen. Some B cells may also carry on their surface IgD as receptor for the antigen. There are many other molecules expressed on the surface of the B cells, which serve different functions. A few of them are B220, class II MHC molecules, CR1 and CR2, CD40, etc.
Activation of B cells
Activation of B cells to produce the full range of antibodies first requires recognition of the epitope by the T-cell-antigen receptor and the production of IL-4 and IL-5 by the helper T cells. In addition, it also requires other co-stimulatory interactions of CD28 on the T cells with B7 on the B cells. The CD28–B7 interaction is essential to produce IL-2. It also includes CD40L on the T cells, which must interact with CD40 on the B cells. The CD40L–CD40 interaction is essential for class switching from IgM to IgG and for switching between other immunoglobulin classes to take place.
Effector functions of B cells
Production of many plasma cells is the end result of activation of B cells. The plasma cells in turn produce large amounts of immunoglobulins specific for the epitope of the antigen. Some activated B cells also produce memory cells, which remain in a stage of quiescence for months or years. Most memory B cells have surface IgG that acts as the antigen receptor, but some even have surface IgM. These quiescent memory cells are activated rapidly on re-exposure to antigen. Memory T cells produce interleukins that facilitate antibody production by the memory B cells. The presence of these cells is responsible for the rapid appearance of antibody in the secondary immune responses.
B-cells respond to two different types of antigen
- Thymus-independent antigens are polymeric molecules which cross-link many specific Ig receptors and provide a persistent signal to the B-cell.
- Thymus-dependent antigens require the co-operation of helper T-cells to stimulate antibody production by B-cells. Antigen captured by specific Ig receptors is taken into the B-cell, processed, and expressed on the surface as a peptide in association with MHC II. This complex is recognized by the T-helper cell, which activates the resting B-cell.