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

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_H (variable region of heavy chain) & V_L (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_H & V_L regions

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

-different B cells have different V_H & V_L 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

-V_H and V_L combine to determine antigen-binding specificity of antibody

-each BCR is bivalent

• 2 antigen-binding sites