W1-7 B lymphocyte development

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50 Questions

Which stage of B cell development is characterized by heavy and light chain rearrangement?

Pre-B cell stage

What is the primary function of RAG-1 and RAG-2 in B cell development?

Catalyzing VDJ recombination

Why is allelic exclusion an important part of B cell rearrangement?

To prevent autoimmune diseases

What distinguishes naïve B cells from memory B cells?

Previous encounter with antigen

Which cell-surface interactions and cytokines are necessary for driving B cell activation and differentiation?

CD40/CD40L interaction and IL-4

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

Enhancement of B cell receptor affinity for antigen

What is the function of Th1 cells in promoting class switching in B cells?

Producing IFN to promote switching to IgG1, IgG2a, and IgG3

Where are the heavy chain locus and the light chain loci located?

Chromosome 2 and chromosome 22

What is the significance of isotype or class switching in B cells?

Allowing the rearranged Vregion to be used with other constant (C)genes than  gene

How many Variable (V) regions are present in the heavy chain locus on chromosome 14?

About 60

What is the role of CD40-CD40L interactions in B cell biology?

Required for isotype or class switching to occur

What do Th2 cells secrete to promote class switching in B cells?

IL-4, IL-5 and TGF-β

What is the function of helper T cells in promoting class switching in B cells?

Promoting class switching to IgG2, IgG4, IgA and IgE

What is the function of Variable region sequences in B cell biology?

Random combination creating at least 1.6 million different antibodies

How does isotype or class switching further recombine the antibody heavy chain genes in B cells?

Allowing the rearranged Vregion to be used with other constant (C)genes than  gene

Which of the following best describes the function of B cells?

Synthesizing and secreting antibodies

What is the primary role of memory B cells?

Providing rapid antibody-mediated immunity

Which surface marker is involved in recognizing C3d fragments deposited on pathogens?

CD21

What is the consequence of failure to achieve tolerance in central tolerance B cells?

Clonal deletion by apoptosis

What is the function of the B cell receptor (BCR)?

Recognizing C3d fragments

Which cells express both IgM and IgD?

Naïve B cells

What happens to activated B cells during differentiation?

Secrete antibodies

Which process allows for more rapid and robust secondary antibody response?

Affinity maturation

Which enzyme plays a role in somatic hypermutation?

AID

What is the role of CD19 in B cell activation?

Mediating intracellular signaling

What happens to activated B cells during differentiation?

Secrete antibodies

Which gene segments are joined in the early Pro-B cell stage?

Heavy chain (DH and JH) gene segments

What is the main event in the late Pro-B cell stage?

Rearrangement of the VH segment to the rearranged DJH segment

What happens to Pro-B cells that fail to produce a functional heavy chain?

They die via apoptosis in the bone marrow

What is formed by the heavy chain, surrogate light chain, Ig, and Igβ in Pro-B cells?

Pre-B cell receptor

What is signaled for transcription to stop upon successful assembly of the pre-B cell receptor complex?

RAG genes

What is the phenomenon termed when the B cell ensures it only expresses one of its two copies of the heavy chain genes?

Allelic exclusion

What reactivates RAG-1 and RAG-2 expression in pre-B cells?

Successful assembly of the pre-B cell receptor complex

What triggers immature B cells to shut down light chain rearrangement?

(BCR) B cell receptor

What occurs when a self-reactive, immature B cell is exposed to self-antigen?

It becomes anergic

What triggers mature B cells to become activated?

Binding of BCR with antigen

When does binding of the BCR with antigen trigger changes in gene expression in the nucleus?

When it binds with protein epitopes on a microorganism

Where does negative selection occur?

Bone marrow

What is the function of protein kinases in the activation of the cell?

Facilitate the first steps of activation

Which cytokines are involved in B-cell activation?

IL-1, IL-4, IL-6, IFN

What is the function of memory B cells?

Enable the host to produce a stronger and faster secondary antibody response

Which surface molecule is synthesized by activated CD4 T cells during B-cell activation?

CD40L

What is the role of CD40 binding to CD40L during B-cell activation?

Induces class switching in activated B cells

Which antigens can activate B cells without requiring T cell help?

Repeating polymers and bacterial cell wall components

What is the function of B-1 cells in the immune system?

Produce low-affinity antibodies and isoantibodies

What surface marker is normally found on immature B cells?

CD5

What is the main function of plasma cells?

Secrete antibodies with high affinity for antigens

Which type of B-cell expresses more sIgD than sIgM?

Conventional B-2 cells

What do activated CD4 T cells secrete to trigger B-cell differentiation?

IL-4 and IL-6

What is the function of CD19 on B-cells?

Express surface immunoglobulins (BCR)

Study Notes

  • B cells are crucial components of the adaptive immune response, responsible for recognizing and responding to antigens, secreting antibodies, and presenting antigens to T cells.
  • Antibodies have five different classes (isotypes), each with unique effector functions and tissue distributions.
  • Immunoglobulin genes undergo adaptive diversity through gene rearrangements, with RAG-1 and RAG-2 responsible for mediating the process.
  • Malfunctions of RAG-1 and RAG-2 result in severe combined immune deficiency (SCID).
  • B cell development consists of several stages: Pro-B to Pre-B cells, where heavy chains form pre-B receptors with surrogate light chains; elimination of self-reactive clones through central and peripheral tolerance; and maturation of B cells.
  • Central tolerance eliminates self-reactive cells in the bone marrow, while peripheral tolerance eliminates self-reactive cells in the periphery.
  • The B cell receptor complex includes the antibody molecule bound to Igα and Igβ, which mediate intracellular signaling, as well as surface molecules CD19, CD20, CD21, and CD81.
  • B cells can be divided into several subsets, such as naïve, activated, plasma cells, and memory cells.
  • Activated B cells undergo differentiation, with plasma cells producing and secreting antibodies, and memory cells providing long-term immunity.
  • Somatic hypermutation, affinity maturation, and isotype switching occur post-activation, resulting in improved antibody production and response to antigens.
  • T helper cells, cytokines, and activation-induced cytidine deaminase AID play essential roles in B cell activation, differentiation, and function.
  • T-independent antigens elicit a different response from B cells compared to T-dependent antigens.
  • B cells express various surface markers with distinct functions.
  • Stem cells commit to the B-lineage in the bone marrow, with B cell development occurring in four phases: generation of B cells, early B cells, pre-B cells, and mature B cells.
  • Early Pro-B cells rearrange heavy chain immunoglobulin genes and express CD19, while later Pro-B cells join the VH segment to the rearranged DJH segment.
  • Rearrangement of heavy chain genes requires RAG-1, RAG-2, and TdT, with unproductive rearrangements leading to apoptosis.
  • Pre-B cells express a pre-B cell receptor with a functional heavy chain and surrogate light chain.
  • Central tolerance eliminates self-reactive cells by negative selection and receptor editing, while peripheral tolerance eliminates self-reactive cells by cell death or anergy.
  • Mature B cells express both IgM and IgD and are considered naïve until they encounter their specific antigen.
  • Activated B cells undergo differentiation into plasma cells, which secrete antibodies, and memory cells, which provide long-term immunity.
  • Memory cells express CD27 and play a role in rapid and robust secondary antibody responses.
  • CD19, CD21, and CD81 are involved in B cell activation and differentiation, with CD19 serving as the signaling chain of the complex.
  • Somatic hypermutation, affinity maturation, and isotype switching lead to improved antibody production and response to antigens, with helper T cells, cytokines, and AID playing essential roles.
  • T-independent antigens elicit a different response from B cells due to their structure and the absence of T cell help.
  • Surface markers on B cells include CD19, CD20, CD21, CD23, CD24, CD27, and IgD, among others, each with distinct functions.

Test your knowledge on the differentiation of B-cells and their activation by specific antigens. Explore the process of B-cell precursor development from bone marrow stem cells and their transformation into functional plasma cell clones.

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