B Cell Development and Activation
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Questions and Answers

Which stage of B cell development involves the rearrangement of heavy chain genes?

  • Pro B cell (correct)
  • Mature B cell
  • Pre B cell
  • Immature B cell

What is the main outcome if immature B cells recognize self-antigen?

  • They mature into plasma cells
  • They undergo apoptosis (correct)
  • They enter circulation as transitional B cells
  • They proliferate into memory B cells

What triggers B cell activation upon encounter with thymus-dependent antigens?

  • Direct contact with TFH cells (correct)
  • Inhibition by CD22
  • Recognition of self-antigens
  • Release of autoantibodies

What is the function of Ig-α/Ig-β in B cell activation?

<p>They initiate signaling through ITAMs (D)</p> Signup and view all the answers

What occurs in the germinal center after B cells are activated?

<p>B cells undergo rapid proliferation to form centroblasts (C)</p> Signup and view all the answers

What is class switching in B cells?

<p>Switching the class of antibody produced (B)</p> Signup and view all the answers

Which type of antigen activates B cells through direct receptor engagement without T cell help?

<p>Thymus-independent antigens (D)</p> Signup and view all the answers

What role does CD22 play in B cell regulation?

<p>Deactivates B cells through ITIM (D)</p> Signup and view all the answers

Which cells are generated from B cells that successfully undergo affinity maturation in the germinal centers?

<p>Plasma cells and memory B cells (B)</p> Signup and view all the answers

What mechanism allows B cells to recognize antigens in peripheral lymphoid tissues?

<p>Membrane-bound Ig associated with BCR (A)</p> Signup and view all the answers

What is the primary mechanism through which B cells achieve a change in antibody specificity?

<p>Somatic hypermutation of V region nucleotides (A)</p> Signup and view all the answers

What initiates class switching in B cells?

<p>Cytokine signaling from T helper cells (D)</p> Signup and view all the answers

How do centrocytes assess their affinity for an antigen in the germinal center?

<p>By comparing their B cell receptor (BCR) affinities to other B cells (B)</p> Signup and view all the answers

Which of the following describes the role of follicular dendritic cells during the germinal center reaction?

<p>Evaluating the affinity of B cells for antigens (A)</p> Signup and view all the answers

What is the primary outcome of a secondary germinal center reaction compared to a primary response?

<p>Enhanced generation of higher affinity antibodies (C)</p> Signup and view all the answers

During the germinal center reaction, which of the following is NOT a function of plasma cells?

<p>Initiating somatic hypermutation (D)</p> Signup and view all the answers

In individuals with X-linked hyper-IgM syndrome, what is the primary defect observed in antibody production?

<p>Exclusively producing IgM antibodies (D)</p> Signup and view all the answers

Which statement best summarizes the outcome of affinity maturation in B cells?

<p>It generates B cells with higher affinity for specific antigens (C)</p> Signup and view all the answers

What role do memory B cells play upon re-infection with a pathogen?

<p>They rapidly divide and generate high affinity antibodies (A)</p> Signup and view all the answers

What is the main reason for the prolonged duration of the germinal center reaction?

<p>To enable continuous assessment of affinity and proliferation (D)</p> Signup and view all the answers

Flashcards

Pro-B cell

The earliest stage of B cell development, characterized by the rearrangement of heavy chain genes (DJ followed by VDJ rearrangements).

Pre-B cell

A stage of B cell development where the cell expresses a surface mu (µ) chain along with a surrogate light chain. Light chain genes rearrange during this stage.

Immature B Cell

A B cell that expresses surface IgM, marking the completion of light chain gene rearrangement.

Mature B Cell

A B cell that expresses both surface IgM and IgD and co-receptor molecules, fully equipped to encounter antigens.

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B Cell Selection

The process by which B cells with receptors that bind to self-antigens are eliminated to prevent autoimmune reactions.

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Transitional B Cell

A B cell that is ready to respond to antigen encounter. These cells are found in the peripheral circulation.

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Thymus-Dependent Antigen (TD)

A thymus-dependent antigen requires direct interaction with T helper cells for B cell activation.

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Thymus-Independent Antigen (TI)

A thymus-independent antigen can activate B cells directly, bypassing the need for T helper cells.

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Type 1 Thymus-Independent Antigen (TI-1)

TI-1 antigens activate B cells through specific pattern recognition receptors, for example, lipopolysaccharide.

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Type 2 Thymus-Independent Antigen (TI-2)

TI-2 antigens are highly repetitive molecules that can activate B cells directly, for example, bacterial flagella.

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Class Switching

Process of changing the antibody class (e.g., from IgM to IgG) by rearranging DNA segments in B cells. This allows the immune system to adapt to different types of infections.

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Germinal Center

A specialized area within secondary lymphoid organs (like lymph nodes) where B cells undergo rapid proliferation, maturation, and differentiation into plasma cells and memory B cells.

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Somatic Hypermutation

Specific mutations that occur in the variable regions of B cell receptor genes. These mutations increase the diversity of antibodies and improve their ability to bind to antigens.

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Affinity Maturation

Increased ability of antibodies to bind to an antigen, achieved through somatic hypermutation and selection within germinal centers.

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Plasma Cells

Mature B cells that produce large amounts of antibody and provide long-lasting immunity.

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Memory B Cells

Long-lived B cells that can rapidly respond to a previously encountered antigen. They provide a quick and powerful immune response upon re-infection.

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Follicular Dendritic Cells (FDCs)

Specialized immune cells that help B cells to undergo class switching by providing signals and cytokines.

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T follicular helper (TFH) cells

Specialized T helper cells that help B cells in the germinal center to mature and produce high-affinity antibodies.

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X-linked hyper-IgM syndrome

A rare genetic disorder caused by a defect in the CD40 ligand (CD40L) gene, leading to an inability to produce antibodies other than IgM.

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Secondary Immune Response

The primary response to an antigen is often slower and less robust compared to a subsequent encounter with the same antigen. This is due to the presence of memory B cells.

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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.

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