T-dependent Humoral response Sp2025

B Lymphocytes

  • B lymphocytes are key components of the adaptive immune system, specifically involved in humoral immunity.

Antigen Recognition and T-Dependent Humoral Response

  • B lymphocytes require help from T-helper (TH) cells for full activation.

Learning Objectives

Lymphocyte Terminology

  • Differentiate among terms related to lymphocytes.

Naïve B Lymphocyte Activation

  • Describe activation processes for naïve B cells in T-dependent manners.

Activation Signals

  • Understand all signals required for B cell activation.

Seeking Help from Effector T Lymphocytes

  • Understand linked recognition in B cell activation process.

T-Dependent Humoral Response

  • Explain the production processes in T-dependent humoral response, including activation, clonal expansion, and differentiation.

Plasma Cell Production Phases

  • Detail the two phases of plasma cell production during the immune response.

Immune Response Timeline

  • Know the timelines and locations of these responses within the lymph node.

Humoral Response Overview

  • Humoral response can be classified as:

    • T-independent: Involving polysaccharide, lipid, and nonprotein antigens.

    • T-dependent: Involving B cells responding to protein antigens, requiring interaction with TH cells and cytokines.

Progression of Lymphocytes (B and T)

  1. Immature lymphocytes lack antigen-specific receptors.

  2. Naive lymphocytes have receptors but have not encountered antigens.

  3. Activated lymphocytes have bound antigens and proliferate.

  4. Effector lymphocytes are the offspring of activated lymphocytes.

  • Plasma cells are the effector cells for B lymphocytes.

  • T cytotoxic and T helper cells serve as effector cells for T lymphocytes.

  1. Memory lymphocytes respond rapidly if the antigen is encountered again.

Anatomy of Lymph Node

  1. Outer Cortex: Contains follicles, mostly B cells along with macrophages and follicular dendritic cells (FDCs).

  2. Paracortex: Mainly T cells and dendritic cells capable of antigen presentation.

  3. Medulla: Drains lymph into efferent lymphatics, containing plasma cells that secrete antibodies during the initial humoral response.

  4. Lymphatic Vessels: Afferent vessels for antigen entry and efferent vessels for lymphocyte exit.

  5. Blood Vessels: Major entry route for B and T lymphocytes into lymph nodes.

T-Dependent Humoral Response Steps

  1. Activation of Naïve B Lymphocyte: Occurs in lymph nodes.

  2. Proliferation: Activated B cells undergo clonal expansion.

  3. Differentiation: B lymphocytes differentiate into effector plasma cells and memory cells.

B cell Activation Process

Required Signals

  1. Antigen binding to BCR (B cell receptor) activates signaling pathways through cross-linking of BCRs.

  2. A second signal is provided by Helper T cells through CD40 and CD40L interactions.

Seeking Help from Helper T Cells

  1. B cells bind to antigen via BCR.

  2. Internalize antigen through receptor-mediated endocytosis.

  3. Present peptide-MHC II complexes to effector helper T cells (TFH).

  4. TFH provides second signal via CD40 ligand, leading to full B cell activation.

Linked Recognition

  • In T-dependent responses, B and T cells recognize different epitopes on the same antigen, facilitating collaboration and response efficacy.

  • This principle is significant for vaccine development and allergy considerations.

Germinal Center Phases of B Cell Activation

Phase 1

  • Some activated B cells move to the medullary region to differentiate into plasma cells secreting IgM.

Phase 2

  • B cells proliferate within the germinal center in the follicular region, undergoing somatic hypermutation and affinity maturation, as well as isotype switching.

Somatic Hypermutation and Affinity Maturation

  • Activated B cells in germinal centers undergo mutations in the variable regions of the BCR L and H chains via the enzyme AID (Activation-induced cytidine deaminase).

  • The mutation rates are significantly higher than normal, occurring at least once per two divisions.

  • B cells with higher affinity for antigens are preferentially selected for survival, enabling affinity maturation.

Differentiation of B Cells in T-Dependent Humoral Response

Positive Selection

  • Selected B cells receive survival signals from TFH through CD40 and cytokines, leading to the differentiation of memory cells and antibody-secreting plasma cells.

Primary vs Secondary Humoral Response

  • Importance of affinity maturation in enhancing the quality of the secondary humoral response, especially in the context of vaccinations.