B Cells and Antibodies

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Questions and Answers

Which of the following represents the most accurate depiction of B cell localization for antigen sampling?

  • B cells are uniformly distributed throughout all bodily tissues, engaging in antigen capture and initiating immune responses at the site of infection.
  • B cells primarily reside in the bone marrow, intercepting antigens that have directly entered the bloodstream during early development.
  • B cell follicles within lymph nodes and the spleen serve as key sites for initial interactions with antigens derived from infected tissues, while marginal zone B cells in the spleen monitor blood antigens. (correct)
  • B cells are predominantly found within the thymic medulla, actively surveying self-antigens to prevent autoimmunity.

Considering the signaling requirements for B cell activation, which statement accurately reflects the current understanding of T-independent and T-dependent responses?

  • Both T-independent and T-dependent responses initiate identically, diverging only in their capacity to induce memory B cell formation, which is exclusively a feature of T-independent activation.
  • T-independent responses necessitate direct interaction with cognate T cells presenting antigen via MHC-II, ensuring high-affinity antibody production through somatic hypermutation.
  • T-independent responses rely on repetitive antigen structures or TLR stimulation, leading primarily to unmutated, low-affinity IgM, while T-dependent responses can involve both early and late responses with potential for somatic hypermutation and class-switching. (correct)
  • T-dependent responses are characterized by early IgM production, lacking somatic hypermutation, and relying exclusively on pathogen-associated molecular patterns (PAMPs) for activation.

Which molecular event is most critical when initiating the intracellular signaling cascade following B cell receptor (BCR) engagement?

  • Internalization of the BCR-antigen complex into early endosomes followed by immediate degradation to prevent excessive signaling.
  • Phosphorylation of Igα/Igβ ITAMs by tyrosine kinases such as SYK, enabling recruitment and activation of downstream signaling molecules. (correct)
  • Immediate translocation of the BCR complex to the nucleus to directly influence gene transcription.
  • Direct activation of NF-κB through conformational changes in the BCR complex, bypassing proximal kinases.

How do B cells strategically patrol for antigens?

<p>B cells strategically patrol areas draining tissues for antigens, particularly within secondary lymphoid organs. (B)</p> Signup and view all the answers

Regarding the cellular pathways of B cell activation, what outcome is associated with NF-κB activation downstream of antigen-induced signaling, CD40L, and TLR signaling?

<p>Class switching. (A)</p> Signup and view all the answers

Marginal zone B cells and B-1 cells both arise from the same developmental pathway and exhibit identical antigen receptor repertoires, primarily targeting polysaccharide antigens in the bloodstream.

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

The B cell receptor (BCR) functions exclusively as a signaling receptor, initiating intracellular cascades upon antigen binding, but lacks any role in antigen internalization or presentation to T cells.

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

Describe the critical distinction in signaling pathways between tonic BCR signaling and antigen-induced BCR signaling, focusing on the differential activation of downstream transcription factors and their ultimate impact on B cell fate.

<p>Tonic BCR signaling promotes sustained, low-level activation of PI3K and subsequent transcription of survival genes, whereas antigen-induced signaling amplifies these signals and additionally activates NF-κB and MAPK pathways, driving proliferation, differentiation, and antibody production.</p> Signup and view all the answers

Explain how the spatial organization of B cell follicles within secondary lymphoid organs facilitates efficient antigen capture and presentation, detailing the roles of follicular dendritic cells (FDCs) and subcapsular sinus macrophages in this process.

<p>B cell follicles are strategically positioned to intercept incoming antigens, with FDCs acting as antigen reservoirs displaying antigens to B cells and subcapsular sinus macrophages capturing and transferring antigens to the follicles, enhancing antigen presentation efficiency.</p> Signup and view all the answers

Delineate the specific roles of the SYK and PI3K kinases in B cell receptor (BCR) signaling, contrasting their immediate substrates and downstream effects on B cell activation and survival.

<p>SYK phosphorylates ITAMs on Igα/Igβ, initiating downstream signaling cascades including PLCγ activation and calcium mobilization. PI3K, activated downstream of CD19, generates PIP3, recruiting and activating proteins such as Akt, promoting B cell survival and proliferation.</p> Signup and view all the answers

B cell activation necessitates two signals: engagement of the BCR by antigen, and either T cell help via the ___________ interaction or signals through _________. These signals dictate proliferation, cytokine secretion and differentiation.

<p>CD40-CD40L, TLRs</p> Signup and view all the answers

Upon B cell activation, the cellular pathway involving PI3K is essential for B cell __________, whereas the combined signaling via NF-kB and MAPK pathways typically drives ___________ and proliferation.

<p>survival, differentiation</p> Signup and view all the answers

Match the following B cell types with their functions:

<p>Follicular B cells = Participate in T-dependent responses, undergoing somatic hypermutation and affinity maturation in germinal centers Marginal zone B cells = Respond rapidly to blood-borne pathogens with T-independent IgM production. Plasma cells = Secrete large quantities of antibodies. Memory B cells = Provide rapid and enhanced secondary antibody responses upon re-exposure to antigen.</p> Signup and view all the answers

Match the following signaling molecules with their corresponding functions in B cell activation:

<p>SYK = Initiates BCR signaling by phosphorylating ITAMs on Igα/Igβ. PI3K = Promotes B cell survival and proliferation via Akt activation. NF-κB = Regulates expression of genes involved in B cell activation, differentiation, and antibody production. MAPK = Contributes to transcriptional regulation and cellular proliferation downstream of BCR signaling.</p> Signup and view all the answers

How does the B cell receptor (BCR) facilitate antigen presentation?

<p>The BCR endocytoses and processes antigen, presenting it via MHC class II molecules to T helper cells. (C)</p> Signup and view all the answers

What is the predominant isotype produced during T-independent B cell responses?

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

Follicular dendritic cells (FDCs) directly stimulate B cells through cognate peptide-MHC interactions, providing a critical signal for B cell activation within germinal centers.

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

Contrast the roles of early and late signaling events following B cell receptor (BCR) ligation in determining B cell fate decisions, focusing on the activation of specific transcription factors and their downstream effects on proliferation, differentiation, and survival.

<p>Early signaling events primarily trigger survival pathways via PI3K/Akt activation, while sustained and amplified signaling leads to activation of NF-κB and MAPK pathways, driving proliferation and differentiation through transcriptional regulation.</p> Signup and view all the answers

The germinal center reaction critically relies on the enzyme ___________, which introduces somatic hypermutations into the immunoglobulin genes, ultimately driving affinity maturation of the B cell response.

<p>activation-induced cytidine deaminase (AID)</p> Signup and view all the answers

Which of the following outcomes is most directly associated with the ability of B cells to present antigen to T helper cells?

<p>Enhanced B cell survival, proliferation, and differentiation into antibody-secreting plasma cells (A)</p> Signup and view all the answers

Flashcards

B cell follicles

Areas in lymph nodes and spleen where B cells interact with antigens.

B cell activation requirements

Requires antigen binding to the BCR and either T cell help OR signals through TLRs.

T-independent responses

Early response antibody, low affinity, and is mostly IgM.

B cell activation summary

B cells patrol draining areas, activation needs two signals, BCR is a receptor, leads to proliferation.

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B cell patrolling

B cells patrol areas draining antigens from tissues.

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T-dependent responses

Both early/late responses and unmutated IgM, but also somatically mutated IgG.

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Memory B cells

Long-lived, more sensitive, higher affinity, class-switched, PC-biased and imprinted by previous activation.

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B cell functions

Three major functions of a B cell are antibody production, cytokine secretion, and antigen presentation.

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Study Notes

B Cells and Antibodies

  • B cell activation involves B cells encountering and responding to their specific antigens

B Cell Localization and Antigen Sampling

  • After development, B cells circulate in secondary lymphoid organs like the lymph nodes, spleen, tonsils, and Peyer's patches to encounter antigens
  • B cell follicles in lymph nodes (LN) and the spleen are primary sites for interactions with antigens coming from infected tissues
  • Marginal zone B cells in the spleen monitor antigens present in the blood

Activation Signals

  • Activation requires two signals: antigen binding to the B cell receptor (BCR) and a second signal, provided either by T cell help or through pathogen-associated molecular patterns (PAMPs) binding to Toll-like receptors (TLRs)

T cell independent response

  • Early response to infection
  • Involves unmutated (low affinity) antibodies, primarily IgM

T cell dependent response

  • Involves both early and late responses
  • Can involve unmutated (low affinity) IgM, but also somatically mutated (high affinity) IgG

Summary of B Cell Activation

  • B cells strategically patrol areas draining antigens from tissues
  • B cell activation requires two signals: antigen binding to the BCR and either T cell help or signals through TLRs
  • The BCR serves as both a signaling receptor and an endocytic receptor for antigen presentation
  • B cell activation leads to proliferation, cytokine secretion, and differentiation into germinal center B cells, plasma cells (PCs), and memory B cells

Cellular Pathways of B Cell Activation

  • Tonic signaling through the BCR sustains B cell survival
  • Antigen-induced signaling initiates a cascade involving Syk, NFκB, Ca2+, MAPK, and PI3K, leading to gene transcription and potentially apoptosis or survival
  • Additional signals like CD40L from T helper cells and cytokines further drive B cell differentiation and class switching

B Cell Functions

  • Antibody production
  • Cytokine Secretion: B cells secrete both pro-inflammatory cytokines (IL-6, TNFα, IL-12, INFγ) and regulatory cytokines (IL-10, TGFβ, IL-35)
  • Antigen Presentation: B cells can present antigens to T cells, further modulating the immune response

Memory B Cells

  • Display characteristics of being long-lived, highly sensitive, class-switched, and PC-biased
  • Further defined by having several subsets imprinted from previous activation

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