Notes on B-cell Development and Immune System Structure

Phase 1: Generation of B-cell Receptors

• Generation: B cells develop various and clonally expressed B-cell receptors (BCRs) in the bone marrow.

Phase 2: Selection of B-cells

• Negative Selection: BCRs that strongly bind to self-antigens are altered, eliminated, or inactivated to prevent autoimmune responses.

Phase 3: Maturation

• Promotion: A select fraction of immature B cells transition into mature B cells located in secondary lymphoid tissues (e.g., lymph nodes, spleen).

Phase 4: Recirculation

• Movement: Mature B cells circulate between lymphatic vessels, blood, and secondary lymphoid tissues, facilitating their immune functions.

Phase 5: Activation

• Clonal Expansion: Activation occurs in secondary lymphoid tissues by pathogen-derived antigens, leading to the proliferation of specific B cells.

Phase 6: Differentiation

• End Stage: Following activation, B cells differentiate into:

  • Plasma Cells: Secrete antibodies to attack infections.

  • Memory B Cells: Provide long-term immunity by residing in the lymphoid tissue.

Overview of the Lymphatic System

• Structure: Comprised of:

  • Venous and arterial systems, heart

  • Lymphatic System Components:

  • Lymphatic ducts and trunks

  • Lymph nodes

  • Collecting lymphatic vessels and capillaries

• Function: Drains tissue fluid, collecting waste for cleanup, and returning it to blood circulation.

Lymphocyte Circulation

• Circulation Mechanism: Lymphocytes exit the blood through high endothelial venules (HEVs) to enter lymph nodes where they encounter antigens and undergo activation.

B-cell Activation Process

1. Naive B Cells enter lymph nodes and encounter matching antigens.

2. T Cell Interaction: T cells provide encouragement for B cell expansion during germinal center reactions.

3. Differentiation: Some B cells evolve into plasma cells, refining immunoglobulin (Ig) affinity through hypermutation.

4. Memory Cells: A portion of B cells becomes memory cells, providing lasting immunity for months to years.

Key Differences in B and T Cell Maturation

• B Cells:

  • Mature in secondary lymphoid tissues after leaving the bone marrow with their BCRs.

• T Cells:

  • Leave the bone marrow without TCRs and complete maturation in the thymus.

Thymus Structure

• The thymus is crucial for T cell development, containing structures such as:

  • Cortex: Contains immature T cells (thymocytes).

  • Medulla: Key for maturing T cells and presenting self-antigens.

• The thymus undergoes involution as individuals age, reducing functional T cell production.

Implications of Aging on Immune Function

• Decreased thymic tissue leads to

  • Reduced T cell generation in the elderly,

  • Differing developmental pathways between B and T cells affecting overall immune strength.