MICB 212 Chapter 5 Notes

B Cells and Antibodies of Adaptive Immunity

Adaptive Immune System

-if innate immunity can’t eliminate infection → adaptive immune system is activated

  • last line of defense

-2 main weapons

  • antibodies

    • produced by B cells

    • main defense against extracellular bacteria

    • protect against infection by viruses

  • T cells

B Cell Development

-derived from common lymphoid progenitors in bone marrow

-remain in bone marrow throughout development and maturation process

-B cells begin expressing B cell receptor (BCR/Igα/Igβ co-stimulatory proteins)

  • responsible for antigen binding

  • determines antigen specificity of B cell

  • Igα/Igβ subunit responsible for sending signals to inside of cell once antigen has been bound

Figure5.1.jpg

B Cell Receptor

-if BCR of immature B cell binds an antigen while still in bone marrow

  • Igα/Igβ co-stimulatory proteins sends signal to inside of cell causing cell to die

-clonal deletion

  • process of eliminating self-reactive B cells

  • analogous to negative selection that thymocytes undergo in thymus

-BCRs don’t need to interact with processed proteins and MHC like TCR of T cells

  • no similar process of positive selection

-undeleted B cells develop to mature B cells that leave bone marrow

  • circulates in blood

  • migrates to spleen and lymph nodes

-BCR of mature, naive B cell is

  • membrane bound immunoglobulin M (mlgM)

    OR

  • membrane bound immunoglobulin D (mlgD)

-each BCR consists of 4 polypeptide chains

  • 2 identical heavy (H) chains

  • 2 identical light (L) chains

-each immunoglobulin H and L chains has

  • 1 variable (V) region

  • 1 constant (C) region

-V(variable region of heavy chain) & V(variable region of light chain) regions combine to form an antigen-binding pocket

  • 2 antigen-binding sites per BCR

-expression of BCR involves rearrangement of immunoglobulin gene segments during development to form complete genes for H & L chain

-single mature B cell has ~100 000 BCRs in membrane

  • all BCRs on a single B cell

-all BCRs have same antigen specificity

  • mlgM and mlgD have same V& Vregions

  • single cell will bind only one or few similar epitopes (antigenic determinants)

-different B cells have different V& VL regions in BCRs → different antigen specificity

  • because different gene segments used when constructing gene for H and L chains

Antibodies/Immunoglobulins (lgs)

-set of proteins made and secreted by B lymphocytes

-antibodies circulate in blood and other body fluids (mucus)

-immunity due to antibodies = humoral immunity

-antibodies bind to macromolecules that are foreign to individual

Antibody Synthesis

-secreted proteins made by B cells

-H and L chain mRNAs are translated into proteins by membrane-bound ribosomes

-H and L chain polypeptides translocated into ER as they are synthesized

-in ER

  • 2 H & 2 L chains joined by disulfide bonds & assembled into complete antibody molecule

-completed antibodies move from ER through Golgi apparatus by vesicular transport

  • vesicles bud off from Golgi apparatus and move towards plasma membrane

-membrane-bound immunoglobulin (mlg) vs secreted antibodies (slgs)

  • amino acid sequences at carboxyl-terminus of H chain

  • mlg: amino acids are hydrophobic

    • polypeptide is anchored in membrane when vesicle fuses with plasma membrane

  • slg: amino acids are hydrophilic

    • antibodies released into extracellular fluids when vesicles with plasma membrane

  • peptides associated with carboxyl-terminus of H chain

    • slg doesn’t associate with Igα/Igβ

-secreted antibodies found mainly in blood

  • also found in bodily secretions

    • GI secretions, mucus secretions, tears, saliva

-B cells secrete antibodies with same specificity as their BCR

Summary

-BCR is surface bound immunoglobulin (mlg) with associated Igα/Igβ component

  • antibodies are secreted immunoglobulin (slg)

-BCR is composed of 4 polypeptide chains (2H and 2L) that are connected by disulfide bonds

  • each polypeptide chain has a variable region and constant region

-Vand Vcombine to determine antigen-binding specificity of antibody

-each BCR is bivalent

  • 2 antigen-binding sites

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