BLOCK 3: IMM: (3.5) B-CELL DEVELOPMENT PART 1

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Questions and Answers

Where do the first three phases of B cell development occur?

Bone marrow (correct)

Thymus gland

Secondary lymphoid tissues

Spleen

What process occurs after the repertoire assembly in B cell development?

Positive selection

Nucleic acid rearrangement

Isotype switching

Negative selection (correct)

What differentiates B1 and B2 lineages in B cell development?

The types of antigens they recognize (correct)

The sites where they are produced

Their stages of positive selection

Their dependence on different cytokines

What is a common misconception about where positive selection occurs for B cells?

Only in bone marrow Signup and view all the answers

Which of the following techniques is NOT related to B cell development?

Transfusion compatibility testing Signup and view all the answers

How do B cells recirculate after development in the bone marrow?

They travel through blood and lymphoid tissues Signup and view all the answers

What is the primary function of somatic hypermutation in B cells?

To adjust B cell receptors for greater diversity Signup and view all the answers

Which phase follows the positive selection of B cells?

Clonal expansion Signup and view all the answers

What is a characteristic of isotype switching in B cells?

It deletes segments of DNA, making it irreversible. Signup and view all the answers

Which statement best describes somatic hypermutation?

It involves point mutations that are not reversed by the body. Signup and view all the answers

What happens to IgD after a B cell encounters an antigen?

It is lost from the surface as the cell matures. Signup and view all the answers

How does transcription regulation relate to B cell activation?

Surface IgM and IgD co-expression affects transcription activity. Signup and view all the answers

What role do point mutations play during somatic hypermutation?

They increase the mutation rate for higher affinity antibodies. Signup and view all the answers

Which aspect of transcriptional elements can be considered irreversible?

Changes due to point mutations in the genetic sequence. Signup and view all the answers

Which statement correctly reflects the relationship between isotype switching and DNA?

It permanently removes gene segments from the DNA. Signup and view all the answers

What technique did Winifred Ashby employ for her research on red blood cells?

Agglutination experiments to determine lifespan. Signup and view all the answers

What is the primary function of B1 cells in the immune system?

To generate antibodies directed against conserved sequences, typically carbohydrates Signup and view all the answers

Why are B1 cells important during fetal development?

They protect the fetus from maternal immune reactions against differing blood types. Signup and view all the answers

How does B1 cell immunity differ from B2 cell immunity?

B1 cells are fewer in number and respond to a more limited range of antigens. Signup and view all the answers

What role do natural antibodies primarily play in the immune response?

They are instinctually produced without previous exposure, targeting blood type antigens. Signup and view all the answers

Which of the following statements is true regarding the discovery of B1 cells?

They were discovered around 20 years ago. Signup and view all the answers

In the context of blood transfusions, how might B1 cells provide an advantage to a fetus?

By preventing maternal rejection of the fetus through natural antibodies against differing blood types. Signup and view all the answers

What is the likely impact of the limited isotype switching associated with B1 cells?

It restricts their ability to adapt to new pathogens. Signup and view all the answers

What is a characteristic feature of B1 cells in terms of their self-renewal capacity?

They can self-renew independently and without T-cell help. Signup and view all the answers

What role does interleukin-7 (IL-7) play in B cell development?

It promotes proliferation and survival of B cell progenitors. Signup and view all the answers

Which of the following signaling molecules is crucial for B cell receptor signaling?

Bruton’s Tyrosine Kinase (BTK) Signup and view all the answers

Which transcription factor is specifically associated with B cell activation?

Pax-5 Signup and view all the answers

What is the function of integrin VLA-4 in B cell development?

It facilitates the binding of B cells to adhesion molecules on stromal cells. Signup and view all the answers

How do interactions between B cells and bone marrow stromal cells influence B cell development?

They promote the transition from pro-B to pre-B cell stages. Signup and view all the answers

What role does the FLT3 protein play in B cell development?

It helps differentiate stem cells into common lymphoid progenitors and B cell progenitors. Signup and view all the answers

What is the specific role of IL-7 in B cell maturation?

It is the receptor for IL-7 that is critical for signaling during early B cell development. Signup and view all the answers

Which of the following proteins is essential for the rearrangement of immunoglobulin genes in B cell development?

TdT Signup and view all the answers

Which polypeptides are known to make up the surrogate light chain in B cell development?

VpreB and λ5 Signup and view all the answers

Which factor is directly associated with the signaling pathway that influences the differentiation of B cell precursors?

FLT3 ligand Signup and view all the answers

What is a primary function of Igα and Igβ in B cell development?

They signal for intracellular processes via their ITAMs. Signup and view all the answers

Which of the following proteins directly binds to the IL-7 receptor in the context of B cell maturation?

Kit Signup and view all the answers

Which stage of B cell development is characterized by the expression of a functional μ chain?

Large pre-B cell Signup and view all the answers

What role does FLT3 signaling play in B cell development?

Promotion of B cell survival and proliferation Signup and view all the answers

How does IL-7 influence B cell maturation?

It enhances lymphocyte proliferation and B cell differentiation Signup and view all the answers

Which of the following signaling molecules is essential for the transition of pro-B cells to pre-B cells?

BTK Signup and view all the answers

What transcription factor is critical for early B cell development and differentiation?

PAX5 Signup and view all the answers

Which of the following best describes the interaction between B cells and bone marrow stromal cells?

Stromal cells provide survival signals and necessary adhesion molecules for B cell maturation Signup and view all the answers

Which CD marker is associated with pro-B cells and may influence differentiation events?

CD10 Signup and view all the answers

What is a common characteristic of both B1 and B2 cells regarding activation pathways?

B2 cells are heavily dependent on helper T cell interactions, whereas B1 cells primarily respond to antigens directly Signup and view all the answers

What is the key function of transcription factors during the differentiation of B cells?

To activate genes necessary for B cell identity and function Signup and view all the answers

Study Notes

B Cell Development

B cell development has six main phases:
- Repertoire assembly (bone marrow)
- Negative selection (bone marrow)
- Positive selection (bone marrow)
- Recirculation (lymphoid tissue)
- Activation (lymphoid tissue)
- Differentiation (lymphoid tissue)
Repertoire assembly forms the B cell receptor.
Negative selection occurs before positive selection.
Reversible modifications:
- Transcriptional elements: irreversible process, involves co-expression of surface IgM and IgD
- IgM and IgD expression: reversible due to loss of IgD after cell circulation
- Splicing: reversible, involves changing the splicing and can be associated with isotype switching
Irreversible modifications:
- Isotype switching: regulated process, occurs with subsequent encounters and cell division
- Somatic hypermutation: point mutations in genomic DNA, not reversible, provides diversity at the antigen-binding site
Phases 1-3 occur in bone marrow
Phases 4-6 occur in secondary lymphoid tissue (lymph nodes, spleen)
B1 cells
- Arise from the fetal liver during embryonic development
- Provide early immune protection for the fetus
- Possess limited isotype switching
- Self-renew
- Almost never requires T-cell help.
- Mostly for conserved sequences, usually carbohydrates on bacteria
- Predominantly found in areas of pathogen encounter (pleural and peritoneal cavities, upper respiratory and GI tract)
- Produce many so-called "natural antibodies"
B2 cells
- Make up the vast majority of B cells in the body.
Natural Antibodies
- Directed against other blood types, potentially protecting the fetus from maternal immune rejection.
Winifred Ashby
- First to establish that red blood cell lifespan in humans is longer than 2-3 weeks
- Used agglutination to determine this.

B Cell Development:

Occurs in 2 phases, 3 in the bone marrow and 3 in secondary lymphoid tissue
The first 3 phases of B cell development take place in the bone marrow.

B Cell Development Markers:

CD127: α chain of the receptor for interleukin-7
CD19: a subunit of the B-cell co-receptor, cooperates with the antigen receptor to produce activating signals when antigen is bound.
CD34: Vascular addressin expressed on endothelial venules in lymph nodes and involved in the extravasation of white blood cells.
CD10: May have a role in inactivating regulatory peptides favoring differentiation events. Normally expressed on pro-B cells and mature germinal center B cells.

B Cell Developmental Stages

Stem cells: Ig genes in the germline configuration
Early pro-B cell: Joining of DH to JH, defined by the rearrangement of the heavy chain, early pro-B cells turn into late pro-B cells
Late pro-B cell: Joining of VH to DJH
Large pre-B cell: Expression of a functional μ chain
Large pre-B cells proliferate, producing small pre-B cells: Rearrangement of the light chain gene occurs
Immature B cell: Successful light-chain gene rearrangement & expression of IgM on the cell surface

Proteins Involved in B Cell Development

FLT3: Protein kinase and cell-surface receptor on stem cells, plays a crucial role in differentiation to CLP and B cell progenitor.
Kit: Acts as a receptor for stem cell factor (SCF)
IL-7R: Receptor for IL-7
RAG proteins: Essential for gene rearrangement, selectively expressed at the 2 stages where rearrangements are made.
TdT: Inserts N nucleotides in the VDJ recombination process.
VpreB & λ5: Polypeptides that form the surrogate light chain.
Igα & Igβ: Have long cytoplasmic tails with ITAMs that interact with intracellular signaling proteins & bind to the immunoglobulin C region on extracellular portions, forming the functional B-cell receptor complex.
CD19: Part of the BCR co-receptor and involved in intracellular signaling.
BTK: Kinase crucial for B cell receptor signaling.
Pax-5: Nuclear transcription factor & B cell-specific activator protein.

B-cell Development: Role of Stromal Cells

Early stages of B-cell development are dependent on bone marrow stromal cells
Stem cells & early pro-B cells use integrin VLA-4 (Very Late Antigen 4) to bind to VCAM-1 (vascular cell adhesion molecule 1) on stromal cells
Interactions of other CAMs promote binding of Kit on the B cell to stem-cell factor (SCF) on the stromal cell
Activation of Kit causes B cell proliferation
Interleukin-7 (IL-7) plays a crucial role in the early development of B cells, promoting proliferation & survival of B cell progenitors during the transition from pro-B to pre-B cell stage.

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Description

Explore the intricacies of B cell development, which encompasses six main phases: repertoire assembly, negative selection, positive selection, recirculation, activation, and differentiation. Understand the reversible and irreversible modifications that influence B cell maturation, including transcriptional elements and isotype switching. This quiz will deepen your understanding of B cell biology in the immune system.