B cells 1 ppt

Light and Dark Zones

  • B Cells 1

  • Emily Gwyer Findlay - e.gwyerfindlay@soton.ac.uk

Overview of B Cells

  • Structure and diversity of B cell receptor and antibodies

  • B cell development and activation

    • In bone marrow

    • In the periphery

  • Antibody subclasses and their functions

  • Plasma cells and memory cells

Learning Objectives

  • Describe the functions and properties of B cells in the immune system

  • Describe the processes involved in B cell development

    • Specificity and diversity

  • Describe the processes involved in B cell activation and differentiation

    • Memory and class switching

Innate vs Adaptive Immunity

Innate Immunity

  • Immediate response to pathogens

  • Targets groups of pathogens through TLR

  • Limited diversity of antigen receptors

  • No memory of pathogens

Adaptive Immunity

  • Gradual response, building over days

  • Targets specific pathogens

  • Highly diverse antigen receptors

  • Produces immunological memory

How the Immune System Works

  • Identification of the pathogen

  • Use of multiple receptors

  • Decision to attack must be coordinated

  • Communication between cells is essential

  • Coordination from tissues like the spleen and lymph node

Relative Activity (Days After Infection)

  • Phagocytes, T Cells, Antibodies, and Cytokines shown over timeline

Differences Between B and T Cells

B Cells

  • Humoral Immunity

  • Arise in the bone marrow

  • Recognize extracellular antigen via B Cell Receptor (BCR)

  • Produce antibodies and long-term memory B cells

T Cells

  • Cellular Immunity

  • Arise in the thymus

  • Recognize native cell-bound antigen via T Cell Receptor (TCR)

  • Produce antibodies and long-term memory

B Cell Responses

Memory Cell

  • Long life span

  • Same BCR as parent cell

Plasma (effector) Cell

  • Lives only a few days

  • Secretes antibodies (2000/sec)

Do We Need B Cells?

Hyper IgM Syndrome

  • Primary immunodeficiency; only express IgM

  • Highly susceptible to infections and cancer

  • Common bacterial infections; severe viral infections

  • Life expectancy under 30 without treatment

Rituximab Treatment

  • Used in lupus; depletes B cells to reduce pathological antibodies

B Cell Receptor (BCR) and Antibody Structure

  • Membrane-bound antibody structure:

    • Two light chains (25KDa) and two heavy chains (50KDa)

    • Variable (V) region and constant (C) region

    • Antigen binding sites found in variable regions

    • Effector function in constant region

BCR Signaling

  • BCR is an antibody and CD79

  • CD79 chains have internal ITAMs that signal cell function

Immunoreceptor Tyrosine-based Activation Motif (ITAM)

  • Plays key role in B cell activation

  • Binds to SH2 domains of protein tyrosine kinases

  • Activation signifies B cell recognition of its antigen

Antibody Structure

  • Isotype determined by carboxy terminus of heavy chain

  • Fab: Fragment Antigen Binding

  • Fc: Fragment Crystallizable

  • Antibody classes: IgM, IgD, IgG, IgA, IgE (with subclasses)

  • Each class has distinct roles and timing of expression

Antibody Maturation Process

  • Occurs in the bone marrow

  • Heavy chain rearrangement followed by light chain rearrangement

  • IgM expressed; negative selection and receptor editing occur

  • Maturation continues in periphery; IgD expressed

  • Class switching occurs in germinal centers of lymph nodes

Role of Stromal Cells in Maturation

  • Essential for B cell progenitor survival

  • VCAM-1 and SCF binding facilitate differentiation

  • IL-7 crucial for B cell survival and proliferation

Generating Antibody Diversity

  • 10 billion different antibody molecules generated

  • Achieved through BCR recombination at three loci for diversity

Recombination in Antibody Development

  1. Heavy chain locus: DJ recombination, VDJ recombination

  2. Pairing with constant domain genes

CDRs and Antibody Diversity

  • Antibodies have Complementarity Determining Regions (CDRs)

  • CDR3 is the most variable, formed by the heavy chain

Negative Selection Process

  • 75% of early B cells self-reactive

  • Apoptosis or receptor editing removes most self-reactive cells

  • Remaining deal with less comprehensive antigen display in periphery

Anergy and Clonal Ignorance

  • Anergy: survival without responsiveness to cognate antigen

  • Maintains clonal ignorance of autoreactive B cells

Summary of B Cell Maturation

  1. Stem cell to B cell progenitor

  2. Pro B cell development with heavy chain recombination

  3. Selection for self tolerance

  4. Migration to spleen and maturation in the periphery