B Cell Ontogeny and Activation

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Questions and Answers

Which process is most closely associated with the progression of B lymphocyte ontogeny?

  • Somatic hypermutation
  • T cell receptor editing
  • Immunoglobulin gene rearrangements (correct)
  • Cytokine storm induction

What is a key function of checkpoint mechanisms during B cell development?

  • To suppress cytokine release
  • To initiate clonal expansion rapidly
  • To promote somatic hypermutation
  • To ensure functional immunoglobulin gene rearrangements (correct)

Which of the following is NOT a typical outcome of B cell activation?

  • Differentiation into plasma cells
  • Differentiation into memory cells
  • Clonal proliferation
  • Apoptosis of the activated cells (correct)

What is the primary role of enzymes during B cell ontogeny?

<p>Mediating DNA recombination during gene rearrangements (B)</p> Signup and view all the answers

Which of the following is not a clearly mentioned learning objective related to B cells?

<p>Describing the process of affinity maturation. (A)</p> Signup and view all the answers

What is the primary function of SDF-1 (CXCL12) in early B cell development?

<p>To retain stem cells and lymphoid progenitors at the surface of bone marrow stromal cells (D)</p> Signup and view all the answers

What is the direct consequence of a failure to successfully rearrange the heavy chain (H chain) genes during B cell development?

<p>Reduction of IL-7 receptor (IL-7R) and induction of apoptosis (A)</p> Signup and view all the answers

The pre-BCR signals drive the proliferation of large pre-B cells, independent of antigen binding, and additionally triggers what process?

<p>L chain gene rearrangements (D)</p> Signup and view all the answers

Which of the following describes the role of Bruton's tyrosine kinase (Btk) during B cell development?

<p>Promotes survival, proliferation, and maturation processes (D)</p> Signup and view all the answers

What is the consequence of signaling through the BCR complex in an immature B cell?

<p>Promotion of cell survival, but not proliferation (B)</p> Signup and view all the answers

Following successful V-J rearrangement, what structural component is expressed by immature B cells?

<p>Fully assembled H+L rearranged IgM structure with Igα and Igβ proteins (A)</p> Signup and view all the answers

Where does negative selection of B cells primarily occur?

<p>Spleen (B)</p> Signup and view all the answers

What is the main function of BAFF (B cell activating factor) during B cell maturation in the spleen?

<p>It promotes survival and maturation of the B cells (A)</p> Signup and view all the answers

What is the average lifespan of a mature naïve B cell, compared to an immature B cell?

<p>Mature B cells have a half-life of 40 days after maturation, while immature B cells is 100 days (C)</p> Signup and view all the answers

Which type of B cell is known for providing a rapid IgM response to blood antigens?

<p>Marginal zone B cells (A)</p> Signup and view all the answers

What is the immediate effect of IL-7 signaling on the developing B cells?

<p>Promotion of survival signals (D)</p> Signup and view all the answers

What is the role of the Kit receptor (CD117) on pro-B cells?

<p>It induces proliferation of the pro-B cells by binding to SCF (A)</p> Signup and view all the answers

What characteristic defines a late pro-B cell?

<p>Successful D-J rearrangement (C)</p> Signup and view all the answers

What is the role of Igα and Igβ proteins on the surface of immature B cells?

<p>They act as signaling molecules after antigen has bound to the IgM (C)</p> Signup and view all the answers

What is characteristic of X-linked Agammaglobulinemia (XLA)?

<p>A mutation resulting in a lack of mature B cells (C)</p> Signup and view all the answers

What is the primary mechanism by which small antigens enter the lymph node (LN)?

<p>Entry through afferent lymphatic vessels via a conduit system. (A)</p> Signup and view all the answers

Which of the following is TRUE regarding follicular dendritic cells (FDC)?

<p>They display antigens on their cell surface for extended periods. (A)</p> Signup and view all the answers

What is the function of Igα and Igβ in the context of B cell receptor (BCR) signaling?

<p>To act as signaling molecules containing ITAMs. (D)</p> Signup and view all the answers

Which of these kinases phosphorylates the ITAMs of Igα and Igβ upon BCR engagement?

<p>Lyn, Fyn, and Blk kinases (D)</p> Signup and view all the answers

What is the role of Syk in B cell activation, similar to its analog in T cells?

<p>To bind to phosphorylated ITAMs and propagate the signal (A)</p> Signup and view all the answers

What is the role of CD21 (CR2) in B cell co-receptor signaling?

<p>To recognize iC3b and C3d derivatives of C3b fragments. (B)</p> Signup and view all the answers

How does CD19 contribute to B cell co-receptor function?

<p>It acts as the signaling chain of the co-receptor. (C)</p> Signup and view all the answers

What is the main role of CD81 in the B cell co-receptor complex?

<p>Binding CD19 and aggregating the co-receptor and BCR. (D)</p> Signup and view all the answers

Which statement best describes the role of complement activation in the context of FDC antigen capture?

<p>C3b attaches to pathogen or antigen and are degraded to C3d. (D)</p> Signup and view all the answers

Where do B-1 B cells primarily reside in the body?

<p>In the peritoneal and pleural cavities. (B)</p> Signup and view all the answers

What is a key characteristic of B-1 B cells regarding T cell help?

<p>They do not require T cell help for antibody production. (B)</p> Signup and view all the answers

Which is the major isotype produced by B-1 B cells?

<p>IgM (B)</p> Signup and view all the answers

Where are marginal zone B cells (MZB) primarily located?

<p>In the marginal zone of the spleen. (B)</p> Signup and view all the answers

Which B cell subtype is responsible for producing a rapid IgM response especially to carbohydrate antigens?

<p>Marginal Zone B cells (B)</p> Signup and view all the answers

Which statement best describes the main difference between follicular B cells (FOB) and B-1 B cells in the context of antigen recognition?

<p>FOB require interaction with CD4+ T cells whereas B-1 B cells do not. (A)</p> Signup and view all the answers

Flashcards

B Cell Ontogeny

The developmental process of B lymphocytes from precursors to mature forms.

Immunoglobulin Gene Rearrangement

The process that allows B cells to produce diverse antibodies by rearranging gene segments.

Checkpoint Mechanisms

Regulatory systems ensuring correct B cell development and function, preventing errors.

Clonal Proliferation

The process by which B cells multiply and create clones in response to antigen exposure.

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B Cell Differentiation

The process where B cells transform into specific types like plasma cells or memory cells.

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B Cell Receptor (BCR)

Membrane-bound immunoglobulin that binds antigens.

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IL-7 in B cell development

Cytokine that promotes B cell survival and development.

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Role of SCF

Stem Cell Factor that binds to Kit for B cell proliferation.

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H chain rearrangement

Process that begins in early pro-B cells to create heavy chains.

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Pre-BCR function

Signals proliferation in large pre-B cells, starts light chain rearrangement.

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X-linked Agammaglobulinemia (XLA)

Genetic disorder resulting in lack of mature B cells and antibodies.

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Immature B cells

B cells that express IgM and leave the bone marrow.

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T1 transitional B cells

In the spleen, they undergo negative selection for self-reactivity.

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Negative selection

Process of eliminating self-reactive B cells.

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BaFF function

B cell activating factor that promotes B cell survival.

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Naïve mature B cells

B cells that have survived selection and are ready to respond.

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Marginal zone B cells

B cells that respond rapidly to blood antigens near the spleen.

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V-J rearrangement

Final step in BCR generation, forming light chains.

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Signal transduction in BCR

Initiates cell survival pathways upon antigen binding.

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Half-life of mature B cells

About 40 days after maturation.

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Ag Flow into LN

Most antigens enter lymph nodes via lymphatics.

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B Cell Recognition

B cells recognize native antigens without modification.

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Follicular Dendritic Cells

FDC capture and display antigens for B cells in lymph nodes.

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BCR Engagement

Binding of B cell receptor (BCR) to antigen activates B cells.

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ITAMs

Immunoreceptor tyrosine-based activation motifs in BCR signaling.

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Syk Kinase

Binds to phosphorylated ITAMs and initiates B cell signaling.

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Co-receptor Signaling

B cell activation requires co-receptors like CD19 and CD21.

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CD19 Function

CD19 enhances signaling from BCR engagement.

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FDC Ag Storage

FDC store and present antigens over long periods to B cells.

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B-1 B Cells

Produce IgM, do not require T cell help, found in cavities.

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B-2 B Cells

Depend on T cell help, produce various antibody isotypes.

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B Cell Diversity

B-1 B cells have low diversity; B-2 B cells have high diversity.

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Memory Production

Follicular B cells produce memory cells; B-1 B cells do not.

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Ag Binding Specificity

B-1 B cells bind carbohydrates; follicular B cells bind proteins.

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Study Notes

B Cell Ontogeny and Activation

  • B cell development begins in the bone marrow
  • Stem cells differentiate into lymphoid progenitor cells
  • Early pro-B cells undergo D-J rearrangement
  • Late pro-B cells complete V-DJ rearrangement
  • Pre-B cells undergo V-J rearrangement
  • Immature B cells express IgM on their surface
  • Immature B cells leave the bone marrow and circulate to the spleen
  • T1 transitional B cells undergo negative selection in the spleen
  • Those B cells that survive negative selection become T2 transitional B cells
  • T2 transitional B cells migrate into follicles in the spleen
  • Interaction with follicular dendritic cells (FDCs) marks B cell maturation to naïve mature B cells
  • Naive B cells can recirculate between lymph, blood, and secondary lymphoid tissues

B Cell Receptors (BCR)

  • BCRs are composed of light and heavy chains
  • BCR recognition involves interaction with antigens
  • Immunoglobulin gene rearrangements lead to BCR diversity
  • BCR crosslinking is essential for B cell activation
  • The BCR signaling complex includes Iga and Igβ and ITAMs
  • BCR activation triggers downstream signaling pathways

B Cell Activation Outcomes

  • Clonal expansion: B cell proliferation and the increase in anti-apoptotic factors
  • Antigen presentation: Increased MHC class I and II presentation and increased co-stimulatory receptors on the B cell
  • Cytokine receptors: Increased cytokine receptors, such as IL-2R, IL-4R, IL-5R, and IL-21R
  • Chemokine receptors: Increased CCR7, and reduced CXCR5 are seen
  • Co-receptor activation increases BCR signaling up to 10,000 fold

These effects depend on various factors and cell types, including follicular dendritic cells and T-helper cells.

B cell Subtypes

  • B-1 cells arise from fetal liver progenitors, primarily in peritoneal and pleural cavities
  • They produce IgM and do not require T cell help for activation
  • The B-1 cells recognize carbohydrate epitopes
  • B-2 (follicular) cells arise from bone marrow progenitors, located in lymphoid tissue follicles
  • They can produce multiple immunoglobulin isotypes (IgM, IgG, IgA, IgE)
  • They need T cell help for full activation
  • Marginal zone B cells are in the marginal zone of the spleen and highly responsive to blood borne antigens
  • These cells produce IgM and do not require T cell help, rapidly responding to carbohydrate antigens.

B cell Maturation Sites

  • Immature B cells leave the bone marrow and arrive at the spleen
  • Immature B cells enter the T cell zone of the white pulp (PALS) becoming transitional B cells (T1)
  • T1 transitional B cells undergo negative selection, recognizing self-antigens and eliminating self-reactive B cells
  • Other T2 transitional B cells migrate into the marginal zone or follicles
  • Marginal zone B cells mature in the marginal sinus zone of the spleen
  • Follicular B cells mature in the lymphoid tissue follicles

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Related Documents

Lec 13: B Cell Ontogeny and Activation (Medical Immunology COM5850) PDF

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