Immune System B Cell Development Quiz

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Questions and Answers

What chemokines attract immature B cells to the lymph node?

CCL21 and CXCL9

CCL22 and CCL17

CXCL12 and CCL19

CCL19 and CCL21 (correct)

How do immature B cells enter the lymph node?

By direct transfer from lymphatic vessels

Through passive diffusion

Via blood capillaries only

Through high endothelial venules (HEV) (correct)

Which specialized cells interact with immature B cells in the lymph node?

Peripheral blood mononuclear cells

Cortical thymic epithelial cells

Follicular dendritic cells (FDC) (correct)

Lymphatic endothelial cells

What role do the chemokines CCL19 and CCL21 play in lymph node architecture?

They aid in the attraction of B cells to lymph nodes Signup and view all the answers

What is the primary function of follicular dendritic cells (FDC) in the lymph node?

To interact with and stimulate immature B cells Signup and view all the answers

What process is responsible for eliminating self-reactive B cells?

Negative selection Signup and view all the answers

What can happen if B cells are over-expressed?

They may contribute to cancer Signup and view all the answers

What is the end result after B cells proliferate and differentiate upon activation?

They produce antibodies Signup and view all the answers

During B cell development, which selection process ensures the generation of B cells with unique B cell receptors (BCRs)?

Positive selection Signup and view all the answers

Which of the following describes the correct trajectory of B cells from activation to function?

Activated B cells become plasma cells and memory B cells Signup and view all the answers

Which gene is associated with Burkitt’s Lymphoma due to its role in cell cycle control?

MYC Signup and view all the answers

What is the primary consequence of a defective BTK in B cell development?

Impaired B cell signaling and maturation Signup and view all the answers

What event can convert a proto-oncogene into an oncogene?

Chromosomal translocation and misexpression Signup and view all the answers

Which of the following types of genes can become oncogenes due to mutation or misregulation?

Proto-oncogenes Signup and view all the answers

How do B cell tumors often arise according to the content provided?

Through chromosomal translocations and oncogene activation Signup and view all the answers

What role does the BCL2 proto-oncogene play in B cell lineage?

Protects from premature apoptosis Signup and view all the answers

Why is the continual production of MYC protein problematic in B cells?

It causes uncontrolled growth and division Signup and view all the answers

What might occur if B cells acquire additional mutations after MYC translocation?

Development of cancer Signup and view all the answers

What factor do immature B cells need to survive and mature in the primary follicle?

CXCL13 Signup and view all the answers

How do most immature B cells die in the primary follicle?

By apoptosis Signup and view all the answers

What is the consequence for mature B cells if they do not encounter a specific antigen?

They die within ~100 days Signup and view all the answers

What is a characteristic of B cell deficiency diseases?

Impaired antibody production Signup and view all the answers

Which condition is associated with a lack of antibodies being produced?

X-linked agammaglobulinemia Signup and view all the answers

What process increases the chance of malignant transformation in B cells?

Lack of interaction between B cells and T cells Signup and view all the answers

What is a common outcome for anergic B cells that enter lymph nodes?

They undergo apoptosis Signup and view all the answers

What is the role of B cell activating factor (BAFF)?

Promotes B cell proliferation and survival Signup and view all the answers

What triggers apoptosis in B cells that fail to competitively enter primary follicles?

Intrinsic molecular defects Signup and view all the answers

Which of the following is NOT considered a B cell tumor?

X-linked agammaglobulinemia Signup and view all the answers

What is the role of dendritic cells in the 2° lymphoid tissue?

Present antigenic peptides with MHC-I and MHC-II Signup and view all the answers

Which signal is NOT required for B cell activation?

Secretion of cytokines by Naïve CD8 T cells Signup and view all the answers

What do activated B cells differentiate into?

Plasma cells and memory B cells Signup and view all the answers

Which of the following is primarily secreted by plasma cells?

High-affinity IgG antibodies Signup and view all the answers

What type of molecules do B cell coreceptors bind to during activation?

C3d on antigens Signup and view all the answers

What is a characteristic of Naïve CD4 T cells when they enter 2° lymphoid tissue?

They are activated by dendritic cells with MHC-II Signup and view all the answers

What is the initial type of antibody secreted by newly activated plasma cells?

IgM Signup and view all the answers

Which statement about B cells is true?

B cells can circulate through all secondary lymphoid tissues. Signup and view all the answers

What is the primary location where B-cell development begins?

Bone marrow Signup and view all the answers

Which of the following stages is characterized by the rearrangement of heavy chain gene segments?

Pro-B cell Signup and view all the answers

What occurs during junctional diversity in B-cell development?

It allows for up to 1.8 million unique combinations Signup and view all the answers

Which component is NOT a part of the pre-B-cell receptor assembly?

IgM antibody Signup and view all the answers

Why do B cells undergo receptor editing?

To ensure self-reactive BCRs are eliminated Signup and view all the answers

What defines positive selection in B cell development?

Failure to bind to self-antigens Signup and view all the answers

Which light chain gene segments are rearranged first during B-cell development?

Kappa light chain segments Signup and view all the answers

What happens to B cells that fail positive selection?

They enter apoptosis Signup and view all the answers

Which of the following describes clonal deletion in B cell development?

Eliminates self-reactive B cells Signup and view all the answers

What is the role of Bone Marrow Stromal Cells in B cell development?

Provide a supportive environment Signup and view all the answers

Which is true about self-tolerant immature B cells?

Leave the bone marrow for maturation Signup and view all the answers

What does allelic exclusion in B cell development ensure?

Each B cell produces monospecific antibodies Signup and view all the answers

During which stage do heavy chain rearrangements predominantly take place?

Pre-B cell Signup and view all the answers

Anergic immature B cells primarily make which of the following?

IgD Signup and view all the answers

Study Notes

Adaptive Immunity: B-Cell Mediated Immunity I

Activation of the Adaptive Immune Response
- Dendritic cells enter secondary lymphoid tissue, presenting antigenic peptides with MHC-I and MHC-II.
- Naïve CD4 T cells enter secondary lymphoid tissue, activated by dendritic cells with MHC-II.
- Naïve CD8 T cells enter secondary lymphoid tissue, activated by dendritic cells (or dendritic cells + TH1) with MHC-I.
- Naïve B cells enter secondary lymphoid tissue, activated by T follicular helper (TFH) cells.

Naïve B Cells

Enter secondary lymphoid tissue from blood/lymph.
Use B cell receptors (BCRs) to scan unprocessed antigens on follicular dendritic cells (or macrophages).
Endocytose BCR:antigen complexes, process, and present peptides with MHC-II to TFH cells.
Activated B cells proliferate and differentiate into plasma cells and memory B cells.
TFH cells provide cytokines (IL-21, IL-6, etc.) to influence this process.
Activation requires 3 signals: BCR and co-receptor cooperation; BCRs cross-linked by intact antigens; B cell co-receptor molecules (CR2, CD19, CD81) bind C3d (on antigen). CD40 binds CD40L on TFH cells.

Plasma Cells = Effector B Cells

Initially secrete low-affinity IgM antibodies.
Some undergo affinity maturation and class switching (to secrete high-affinity IgG or other antibody classes).

BCR Gene Structure

Germline configuration of BCR/immunoglobulin genes inherited from egg and sperm.
Fragmented into several gene segments (L, V, D, J, C); multiple alleles.
Expression requires segment rearrangement and assembly into one complete functional gene.

BCR Gene Segments

Heavy-chain locus on chromosome 14: VH1, VH2, VH3, DH1-23, JH1-6, CH1-9.
Light-chain locus (к on chromosome 22; λ on chromosome 2): different Vs, Js, C segments.

Constant (C) Region Genes

Light chain: 4 or 5 Cᵝ gene segments possible.
к light chain: only 1 CR possible gene segment.
Heavy chain: 9 CH possible gene segments.

Somatic Recombination

Cutting and splicing of immunoglobulin gene segments during B cell development.
Light chain: one recombination event (~V+J).
Heavy chain: two recombination events (~D+J then V+DJ).
Creates diversity in antigen-binding sites in BCR and immunoglobulin.

Recombination Signal Sequences (RSSs)

Short DNA sequences flanking V, J, and D gene segments.
12/23 rule: recombination occurs between two RSSs with different length spacers (12 & 23).

V(D)J Recombinase

Complex of enzymes carrying out somatic recombination in B cells.
RAG-1 and RAG-2 proteins are essential.
Cleaves RSSs at end of each heptamer; DNA ends recombined.
Coding joint creates functional V region exon.
Signal joint circularizes excised DNA.

Junctional Diversity

DNA sequence variations created in coding joints during V(D)J recombination.
Adds additional diversity to antigen-binding sites.
Includes P nucleotides (palindromic) and N nucleotides (non-templated) generated by terminal deoxynucleotidyl transferase (TdT).

B-Cell Tolerance: Receptor Editing and Anergy

Receptor editing mechanisms in immature B cells.
Recognize multivalent self-antigens, decreasing IgM and continuing to rearrange light chain genes.
New BCR is self-tolerant, the immature B cell matures.
New BCR is self-reactive then the process continues until a self-tolerant BCR is produced or cell runs out of light chain genes (apoptosis).
Anergy mechanisms in immature B cells recognizing monovalent self-antigens.
Make IgM and IgD but not active BCR.
Most die within one to five days.

B-Cell Maturation and Survival

Occurs in lymphoid follicles in secondary lymphoid tissues.
Immature B cells interact with follicular dendritic cells (FDCs) to complete maturation.
Mature B cells interact periodically with FDCs to survive.
Die in ~100 days if specific antigen not encountered.

B-Cell Abnormalities

B-cell deficiencies (X-linked agammaglobulinemia, X-linked immunodeficiency with hyper-IgM, etc.) can lead to problems with antibody production.
B-cell tumors feature uncontrolled growth and proliferation often linked to chromosomal translocations and proto-oncogenes activation.

Proto-oncogenes to Oncogenes

Proto- oncogenes (normal genes) regulate cell growth and division.
Mutations can transform them into oncogenes (cancer-causing genes), which are overexpressed, leading to uncontrolled proliferation.

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Description

Test your knowledge on the role of chemokines and specialized cells in the development of B cells within the lymph node. This quiz covers the processes involved in B cell selection, activation, and their functions, including associated pathologies like Burkitt’s Lymphoma.