Micro 204

Flipped Classroom Session

Antibodies

IgE and IgA

Chris Allen Tony DeFranco

IgE Antibody Function

mast cell or basophil

FcεRI

IgE including histamine chemokines cytokines

mediators

inflammation

Parasitic worm

Normal Functions of Antibodies Neutralization

toxins

viruses

Mast cell

Parasitic worm

inflammation

bacteria Complement activation

Macrophage bacteria

Opsonization

Toxic granules Foreign/ infected

cell

Antibody-dependent cytotoxicity

IgG

IgE

IgM

IgA

IgG

IgG

Differences in Fc Receptors

Macrophage

bacteria

FcγR

Mast Cell FcεRI

IgE IgG

Changes in Antibodies n  Class switch recombination

•  Membrane vs secreted

mutation, selection

Low affinity

High affinity

•  Affinity maturation

IgE Constant region (function)

Variable region (antigen-binding)

Transmembrane & Intracellular

Domains

B cell Plasma cell

IgG

IgE IgM IgD

IgA AID

B Cell Differentiation Pathways

Germinal Center

Activated B Cell

Short-Lived Plasma Cell

Affinity Maturation Hypermutation, Selection

Long-Lived Plasma Cell

Memory B Cell

Germinal Center Selection

Plasma Cell

Memory B Cell

Antigen

highest affinity

BCR signal

T cell T cell help GC

B Cells

Differentiation

highest affinity

Proliferation

Apoptosis

Helminth parasite model: Nippostrongylus brasiliensis infection

Differences in Kinetics of Antibody Responses Infection N. brasiliensis L3 larvae

Erazo A. et al. Immunity 2007, 26:191-203.

Cheng L.E. et al. J Immunol 2010, 185:5040-5047.

Differences in IgG1 vs IgE Germinal Center B Cell Responses

N. brasiliensis infection

Talay O. et al. Nat Immunol 2012, 13:396-404.

Yang Z. et al. Immunity 2012, 36:857-872.

He J.S. et al. J Exp Med 2013, 210:2755-2771. Similar data in:

IgG1+ Germinal Center B Cells IgE+ Germinal Center B Cells

Questions

n  Why do IgE+ B cells disappear from the germinal center?

n  What are the implications for the IgE antibody response?

Why IgE B cell lifespan and affinity may be limited

Neutralization

toxins

viruses

Mast cell

Parasitic worm

inflammation

IgG IgE IgA

Systemic IgE

activation