B Cell Activation And Antibody Production Ppt
Start studying B Cell Activation & Antibody Production. Learn vocabulary, terms, and more with flashcards, games, and other study tools.
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 According to research conducted by HCI and Oracle and released in early 2015, 60 percent of 291 employers said workers who were promoted into jobs performed significantly better than employees. Created Date: 3:42:32 PM. Focus marzo 2015 pdf map. 2015 FoCuS+ ST ford.com epa-eSTimaTed raTing 32 hwy mpg 3 0–60 6.4 SeC.4 270lb.-f t. Tangerine Scream Tri-coat Metallic. Available equipment. 1Using 93-octane fuel.2Available feature. 3EPA-estimated rating: 23 city/32 hwy/26 combined mpg, 2.0L EcoBoost.Actual mileage will vary. 4Based on Ford testing with standard summer tires. Start taking the street by storm. Research the 2015 Ford Focus at cars.com and find specs, pricing, MPG, safety data, photos, videos, reviews and local inventory. | 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+ |
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. Sims 3 saddle pad.
(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.
T independent antigen elicits antibody production by B lymphocytes without T lymphocyte involvement. There are 2 distinct subgroups of TI antigens, different in mechanism of activating B lymphocytes. TI-1 antigen, which has an activity that can directly activate B cells and TI-2 antigen, which has highly repetitive structure and causes simultaneous cross-linking of specific B cell receptors (BCR) on B lymphocyte. The most commonly released isotype of antibodies in this type of immune reaction is low affinity IgM.[1]
Antibody production independent of T lymphocytes[edit]
For most protein antigens, the production of antibodies by B lymphocytes is dependent on stimulation of helper T cells. However bacterial polysaccharides and lipopolysaccharides, and some polymeric proteins, can stimulate B lymphocytes without involvement of helper T cells. The non-protein microbial antigens can not stimulate classical T cell response by themselves, but they are able to elicit the production of antibodies, so that is why we call them T cell or thymus independent antigens.[2]
T independent antigens are divided into 2 classes by the mechanism of activating B cells.
TI-1 antigen[edit]
TI-1 antigens have an intrinsic B cell activating activity, that can directly cause proliferation and differentiation of B lymphocytes without T cell stimulation and independently of their BCR specificity. TI-1 antigens activate B-cells via Toll like receptors, which are, in human, expressed on the surface of B lymphocytes after BCR stimulation. TI-1 antigens are classified as B-cell mitogens, because they induce numerous cell divisions. In higher concentrations, TI-1 antigens bind to BCR and TLR of various clones of B lymphocytes, which leads to production of multiclonal antibodies. But when the concentration of TI-1 is lower, it can activate only B lymphocytes with specific binding of TI-1 on their BCR, and leads to production of monoclonal antibodies.[1]This part of immune response may be important in some early stages of infection by extracellular pathogens, because it is rapidly activated and does not require T cell help or clonal maturation and expansion. An example of TI-1 antigen is lipopolysaccharide (LPS) or bacterial DNA.[2]
TI-2 antigen[edit]
Second group of TI antigens consists mainly of highly repetitive surface structures (epitopes) of encapsulated bacteria. They do not have an intrinsic B-cell activating activity. The activation of B lymphocytes is caused by cross-linking of a critical number of B cell receptors, which leads to accumulation of BCRs and cross activation of these receptors. It results in proliferation and differentiation of B lymphocytes and production of antibodies. TI-2 antigens can activate only mature B lymphocytes. Immature B cells are anergized, so they do not elicit any immune response. That may explain why children up to 5 years are not capable of producing effective antibodies against polysaccharide antigens, as the majority of their B cell population is immature.[2]Even though the response on TI antigens is not dependent on T lymphocytes, there are some cytokines, produced mainly by T lymphocytes and natural killer (NK) cells, necessary for eliciting reaction against these antigens. The most necessary are interleukin 2 (IL-2), interleukin 3 (IL-3) and interferon γ (IFN-γ).[1] Moreover, additional stimulation by dendritic cells (DC) and macrophages is required.[2]
References[edit]
- ^ abcHOŘEJŠÍ, Václav. Základy imunologie. 5. vyd. Praha: Triton, 2013, 330 s. ISBN978-80-7387-713-2.
- ^ abcdMURPHY, Kenneth. Janeway's immunobiology. 8th ed. London: Garland Science, c2012, xix, 868 s. ISBN978-0-8153-4530-5.