Podcast
Questions and Answers
Which stage of B cell development involves the rearrangement of heavy chain genes?
Which stage of B cell development involves the rearrangement of heavy chain genes?
What is the main outcome if immature B cells recognize self-antigen?
What is the main outcome if immature B cells recognize self-antigen?
What triggers B cell activation upon encounter with thymus-dependent antigens?
What triggers B cell activation upon encounter with thymus-dependent antigens?
What is the function of Ig-α/Ig-β in B cell activation?
What is the function of Ig-α/Ig-β in B cell activation?
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What occurs in the germinal center after B cells are activated?
What occurs in the germinal center after B cells are activated?
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What is class switching in B cells?
What is class switching in B cells?
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Which type of antigen activates B cells through direct receptor engagement without T cell help?
Which type of antigen activates B cells through direct receptor engagement without T cell help?
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What role does CD22 play in B cell regulation?
What role does CD22 play in B cell regulation?
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Which cells are generated from B cells that successfully undergo affinity maturation in the germinal centers?
Which cells are generated from B cells that successfully undergo affinity maturation in the germinal centers?
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What mechanism allows B cells to recognize antigens in peripheral lymphoid tissues?
What mechanism allows B cells to recognize antigens in peripheral lymphoid tissues?
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What is the primary mechanism through which B cells achieve a change in antibody specificity?
What is the primary mechanism through which B cells achieve a change in antibody specificity?
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What initiates class switching in B cells?
What initiates class switching in B cells?
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How do centrocytes assess their affinity for an antigen in the germinal center?
How do centrocytes assess their affinity for an antigen in the germinal center?
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Which of the following describes the role of follicular dendritic cells during the germinal center reaction?
Which of the following describes the role of follicular dendritic cells during the germinal center reaction?
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What is the primary outcome of a secondary germinal center reaction compared to a primary response?
What is the primary outcome of a secondary germinal center reaction compared to a primary response?
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During the germinal center reaction, which of the following is NOT a function of plasma cells?
During the germinal center reaction, which of the following is NOT a function of plasma cells?
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In individuals with X-linked hyper-IgM syndrome, what is the primary defect observed in antibody production?
In individuals with X-linked hyper-IgM syndrome, what is the primary defect observed in antibody production?
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Which statement best summarizes the outcome of affinity maturation in B cells?
Which statement best summarizes the outcome of affinity maturation in B cells?
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What role do memory B cells play upon re-infection with a pathogen?
What role do memory B cells play upon re-infection with a pathogen?
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What is the main reason for the prolonged duration of the germinal center reaction?
What is the main reason for the prolonged duration of the germinal center reaction?
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Study Notes
B Cell Development and Activation
- B cell development occurs in the bone marrow
- B cells originate from a common hematopoietic stem cell
- B cell development has four recognized stages
- Pro-B cell: the initial B cell progenitor, characterized by heavy chain gene rearrangement (DJ then VDJ).
- Pre-B cell: expresses a μ chain associated with a surrogate light chain, with further light chain gene rearrangement
- Immature B cell: expresses IgM on its surface
- Mature B cell (naive B cell): expresses both IgM and IgD and B cell co-receptor
- Immature B cells circulate to peripheral lymphoid organs (e.g., spleen, lymph nodes)
- During development, cells undergo selection to eliminate those producing antibodies against self-antigens. Cells that recognise self-antigens undergo apoptosis
- Mature B cells either become B1, marginal zone or follicular cells over days
B Cell Activation
- Activation occurs when B cells encounter antigens
- Membrane-bound antibodies have short cytoplasmic tails, too short to generate signals alone.
- Signals are generated by associating with tyrosine kinases and G proteins
- Membrane Ig must be associated with B cell receptor
- Ig-α/lg-β have ITAMs (immunoreceptor tyrosine activation motifs)
- Thymus-dependent (TD) antigens:
- Require direct contact with T helper cells (TFH)
- Thymus-independent (TI):
- Type 1: lipopolysaccharides (LPS)
- Type 2: highly repetitive molecules (e.g., bacterial flagella)
- B cells recognising antigen in lymphoid tissue via BCR and receive co-stimulatory signals from TFH cells
Germinal Center Events
- Activated B cells migrate to the germinal center of secondary lymphoid tissues
- Somatic hypermutation: point mutations in V regions alter antibody specificity, resulting in improved affinity to the antigen.
- Class switching: DNA rearrangement allows for the production of different antibody classes
- Affinity maturation: tests for the best-fitting antibody to the antigen. B cells with high affinity for the antigen survive, improving the immune response over time
- Centrocytes become either plasma cells or memory cells. Plasma cells secrete antibodies, while memory B cells remain to quickly mount an immune response to future infections
- Reactions monitored by follicular dendritic cells (FDCs) and TFH cells.
- B cell survival is determined by affinity of antibodies to antigen. High-affinity cells survive longer
Class Switching
- Dependent on cytokines to switch antibody isotypes from IgM to other antibodies (IgG, IgA, or IgE)
- Interaction of CD40 on B cells and CD40L on T cells important in switching
- X-linked hyper-M syndrome: defective CD40L or interaction with CD40
- TH cells not expressing CD40L, patients only produce IgM. No memory cell populations observed.
Summary
- Antigen encounter leads to B cell activation, involving antigen recognition, co-stimulation, and cytokine signaling
- Activation results in germinal center formation in secondary lymphoid tissues. B cells undergo proliferation, affinity maturation and class switching
- Class switching changes the antibody class a B cell produces (e.g., from IgM to IgG, IgA, or IgE) through recombination between switch regions.
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Description
Explore the intricate processes of B cell development and activation. This quiz covers the stages of B cell maturation, their migration to lymphoid organs, and the mechanisms of B cell activation upon encountering antigens. Test your knowledge on the fundamentals of immune response and B cell functionality.
