B Cells and Antibodies Lecture Notes

Introduction to B Cells

• Lecture Focus: Understanding B cells and antibodies

• Objectives:

  • Describe structure of antibodies and their function

  • Understand how antibodies work

  • Explore B cell development

  • Learn steps in the T-dependent B cell response

B Cells Overview

• Transition from innate to adaptive immune system

• Hematopoiesis:

  • Hematopoietic stem cells differentiate into myeloid progenitors and lymphoid progenitors

  • B cells arise from lymphoid progenitors

• Role of B cells:

  • Mediators of humoral immunity (involves antibodies, complement proteins, antimicrobial peptides)

  • Responsible for producing antibodies that neutralize and eliminate extracellular microbes and toxins

Importance of B Cells

• Absence of B cells leads to:

  • No antibody production

  • Conditions like X-linked Agammaglobulinemia result in no B cells, leading to severe recurrent bacterial infections and poor vaccination responses.

Understanding Antibodies

• Structure and Function:

  • Antibodies are derived from B cell receptors, which start as membrane-bound immunoglobulins.

  • B cell receptors can bind specifically to antigens; each B cell expresses thousands of identical receptors.

  • Clonal expansion occurs after activation to produce enough cells to combat pathogens.

• Types of Antigen Recognition:

  • B cells can recognize a diverse range of antigens including proteins, lipids, carbohydrates, and nucleic acids in their native forms.

Antibody Structure

• Basic Components:

  • Y-shaped molecules composed of four polypeptide chains: two heavy chains and two light chains

  • Regions:

    • Variable region (binds antigens)

    • Constant region (defines antibody's isotype)

  • Antibodies are classified into five isotypes: IgG, IgA, IgM, IgE, IgD

• Fragmentation Mechanism:

  • Papain and pepsin enzymes digest antibodies into FAB (antigen-binding fragment) and FC (fragment crystallizable) regions.

Antibody Isotypes and Functions

• Isotypes:

  • IgM: first antibody produced, forms pentamers, provides high avidity.

  • IgG: most abundant in serum, has various functions and subclasses with significant roles in neutralization, opsonization, and complement activation.

  • IgA: dominant in mucosal tissues, critical for neutralizing pathogens.

  • IgE: important in immune responses to parasites and allergies.

Antibody Functions

• Neutralization:

  • Binding to pathogens to block infection or to block toxins.

• Opsonization & Phagocytosis:

  • Coating pathogens to enhance phagocytosis by macrophages and other cells.

• Antibody-Dependent Cellular Cytotoxicity (ADCC):

  • Involvement of natural killer cells to target and destroy infected cells.

• Complement Activation:

  • Antibodies activate complement pathways leading to pathogen lysing.

B Cell Development

• Development occurs primarily in the bone marrow:

  • Commitment to B cell lineage and rearrangement of B cell receptor genes.

  • V(D)J recombination creates diverse receptor specificity via combinatorial and junctional diversity.

  • Positive and negative selections ensure self-tolerance and functional viability.

• Migration to spleen for final maturation where they become either follicular or marginal zone B cells.

B Cell Activation

• Activation can be T-independent (short-lived, IgM) or T-dependent (long-lived, isotype-switching antibodies).

• T-dependent responses involve:

  • Interaction with T cells using CD40 and cytokines.

  • Formation of germinal centers for affinity maturation and further differentiation.

• Memory B cells and long-lived plasma cells are generated for long-term immunity.

Conclusion

• B cells are essential for adaptive immunity, producing antibodies with diverse functionalities, and capable of adapting through processes like somatic hypermutation and isotype switching.

• Understanding B cell activation and function is crucial for comprehending vaccine responses and immune defense against pathogens.