B-Cell Generation, Activation, and Differentiation.
Transcript of B-Cell Generation, Activation, and Differentiation.
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B-Cell Generation,Activation, andDifferentiation
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The developmental process that results in production of plasma cells and memory B cells can be divided into three broad stages:
1.Generation of mature, immunocompetent B cells (maturation).
2.Activation of mature B cells when they interact with antigen.
3.Differentiation of activated B cells into plasma cells and memory B cells.
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1. B-Cell Maturation
Overview of B-cell development. During the antigen- independent maturation phase, immunocompetent B cells expressing membrane IgM and IgD are generated in the bone marrow. Only about 10% of the potential B cells reach maturity and exit the bone marrow. Naive B cells in the periphery die within a few days unless they encounter soluble protein antigen and activated TH cells. Once activated, B cells proliferate within secondary lymphoid organs. Those bearing high-affinity mIg differentiate into plasma cells and memory B cells, which may express different isotypes because of class switching. The numbers cited refer to B-cell development in the mouse, but the overall principles apply to humans as well.
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1) Progenitor B Cells Proliferate in Bone Marrow
Bone-marrow stromal cells are required for maturationof progenitor B cells into precursor B cells.
Progenitor B cell (pro-B cell) precursor B cells (pre-B cells)
stem cell factor (SCF)
VCAM-1 :Vascular cell adhesion molecule-1
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2) Ig-Gene Rearrangment Produces Immature B Cells
Sequence of events and characteristics of the stagesin B-cell maturation in the bone marrow.
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3) The Pre–B-Cell Receptor Is Essential for B-Cell Development
Schematic diagram of sequential expression of membrane immunoglobulin and surrogate light chain at different stages of B-cell differentiation in the bone marrow.
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4) Self-Reactive B Cells Are Selected Against in Bone Marrow
Experimental evidence for negative selection (clonal deletion) of self-reactive B cells during maturation in the bone marrow.
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2.B-Cell Activation and Proliferation
After export of B cells from the bone marrow, activation, proliferation, and differentiation occur in the periphery and require antigen. Antigen-driven activation and clonal selection of naive B cells leads to generation of plasma cells and memory B cells. In the absence of antigen-induced activation, naive B cells in the periphery have a short life span, dying within a few weeks by apoptosis.
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1) Thymus-Dependent and Thymus- Independent Antigen Have Different Requirements for Response
Depending on the nature of the antigen, B-cell activation proceeds by two different routes, one dependent upon TH cells, the other not. The B-cell response to thymus-dependent (TD) antigens requires direct contact with TH cells, not simply exposure to TH-derived cytokines. Antigens that can activate B cells in the absence of this kind of direct participation by TH cells are known as thymus-independent (TI) antigens.
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TI antigens are divided into types 1 and 2, and they activate B cells by different mechanisms. Some bacterial cell-wall components, includinglipopolysaccharide (LPS), function as type 1 thymus-independent (TI-1) antigens. Type 2 thymus-independent (TI-2) antigens are highly repetitious molecules such as polymeric proteins (e.g., bacterial flagellin) or bacterial cell-wall polysaccharides with repeating polysaccharide units.
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2) Two Types of Signals Drive B Cells into and Through the Cell Cycle
An effective signal for B-cell activation involves twodistinct signals induced by membrane events.
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3) Transduction of Activating Signals Involves Ig-/Ig- Heterodimers
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Some of the many signal-transduction pathwaysactivated by the BCR.
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4) The B-Cell–Coreceptor Complex Can Enhance B-Cell Responses
The B-cell coreceptor is a complex of three cell membranemolecules:
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5) TH Cells PlayEssential Rolesin Most B-Cell Responses
Sequence of events in B-cell activation by a thymus-dependent antigen.
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Transmission electron micrographs of initial contact between a T cell and B cell (left) and of a T-B conjugate (right). Note the broad area of membrane contact between the cells after formation of the conjugate.
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This section considers the differences between the primaryand secondary humoral response and the use of haptencarrierconjugates in studying the humoral response.
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3.The Humoral Response
1) Primary and Secondary Responses Differ Significantly
Concentration and isotype of serum antibody following primary (1°) and secondary (2°) immunization with antigen.
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2) T Helper Cells Play a Critical Role in the Humoral Response to Hapten-Carrier Conjugates
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4.Germinal Centers and Antigen- Induced B-Cell Differentiation
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