W1-7 B lymphocyte development
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W1-7 B lymphocyte development

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@alexreed7

Questions and Answers

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?

<p>Previous encounter with antigen</p> Signup and view all the answers

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

<p>CD40/CD40L interaction and IL-4</p> Signup and view all the answers

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

<p>Enhancement of B cell receptor affinity for antigen</p> Signup and view all the answers

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

<p>Producing IFN to promote switching to IgG1, IgG2a, and IgG3</p> Signup and view all the answers

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

<p>Chromosome 2 and chromosome 22</p> Signup and view all the answers

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

<p>Allowing the rearranged Vregion to be used with other constant (C)genes than  gene</p> Signup and view all the answers

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

<p>About 60</p> Signup and view all the answers

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

<p>Required for isotype or class switching to occur</p> Signup and view all the answers

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

<p>IL-4, IL-5 and TGF-β</p> Signup and view all the answers

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

<p>Promoting class switching to IgG2, IgG4, IgA and IgE</p> Signup and view all the answers

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

<p>Random combination creating at least 1.6 million different antibodies</p> Signup and view all the answers

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

<p>Allowing the rearranged Vregion to be used with other constant (C)genes than  gene</p> Signup and view all the answers

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

<p>Synthesizing and secreting antibodies</p> Signup and view all the answers

What is the primary role of memory B cells?

<p>Providing rapid antibody-mediated immunity</p> Signup and view all the answers

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

<p>CD21</p> Signup and view all the answers

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

<p>Clonal deletion by apoptosis</p> Signup and view all the answers

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

<p>Recognizing C3d fragments</p> Signup and view all the answers

Which cells express both IgM and IgD?

<p>Naïve B cells</p> Signup and view all the answers

What happens to activated B cells during differentiation?

<p>Secrete antibodies</p> Signup and view all the answers

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

<p>Affinity maturation</p> Signup and view all the answers

Which enzyme plays a role in somatic hypermutation?

<p>AID</p> Signup and view all the answers

What is the role of CD19 in B cell activation?

<p>Mediating intracellular signaling</p> Signup and view all the answers

What happens to activated B cells during differentiation?

<p>Secrete antibodies</p> Signup and view all the answers

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

<p>Heavy chain (DH and JH) gene segments</p> Signup and view all the answers

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

<p>Rearrangement of the VH segment to the rearranged DJH segment</p> Signup and view all the answers

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

<p>They die via apoptosis in the bone marrow</p> Signup and view all the answers

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

<p>Pre-B cell receptor</p> Signup and view all the answers

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

<p>RAG genes</p> Signup and view all the answers

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

<p>Allelic exclusion</p> Signup and view all the answers

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

<p>Successful assembly of the pre-B cell receptor complex</p> Signup and view all the answers

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

<p>(BCR) B cell receptor</p> Signup and view all the answers

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

<p>It becomes anergic</p> Signup and view all the answers

What triggers mature B cells to become activated?

<p>Binding of BCR with antigen</p> Signup and view all the answers

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

<p>When it binds with protein epitopes on a microorganism</p> Signup and view all the answers

Where does negative selection occur?

<p>Bone marrow</p> Signup and view all the answers

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

<p>Facilitate the first steps of activation</p> Signup and view all the answers

Which cytokines are involved in B-cell activation?

<p>IL-1, IL-4, IL-6, IFN</p> Signup and view all the answers

What is the function of memory B cells?

<p>Enable the host to produce a stronger and faster secondary antibody response</p> Signup and view all the answers

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

<p>CD40L</p> Signup and view all the answers

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

<p>Induces class switching in activated B cells</p> Signup and view all the answers

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

<p>Repeating polymers and bacterial cell wall components</p> Signup and view all the answers

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

<p>Produce low-affinity antibodies and isoantibodies</p> Signup and view all the answers

What surface marker is normally found on immature B cells?

<p>CD5</p> Signup and view all the answers

What is the main function of plasma cells?

<p>Secrete antibodies with high affinity for antigens</p> Signup and view all the answers

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

<p>Conventional B-2 cells</p> Signup and view all the answers

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

<p>IL-4 and IL-6</p> Signup and view all the answers

What is the function of CD19 on B-cells?

<p>Express surface immunoglobulins (BCR)</p> Signup and view all the answers

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.

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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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