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T and B Cell Costimulation. Robert H. Carter, MD rcarter@uab.edu Div. Rheumatology, Dept. Medicine Dept. Microbiology Program in Cellular and Molecular Biology Program in Immunology University of Alabama at Birmingham. Germinal Center, WT CD19, SRBC Day 7 . Red pulp. FDC. Germinal

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t and b cell costimulation

T and B Cell Costimulation

Robert H. Carter, MD

rcarter@uab.edu

Div. Rheumatology, Dept. Medicine

Dept. Microbiology

Program in Cellular and Molecular Biology

Program in Immunology

University of Alabama at Birmingham

slide2

Germinal Center, WT CD19, SRBC Day 7

Red pulp

FDC

Germinal

Center

Marginal zone

Marginal Sinus

Endothelial cell

Central

arteriole

PNA Alexa 488 GreenCD35 Alexa 350 Blue

Ki-67 Alexa 555 RedIgD Bio SA-Cy5 gold

slide3

Memory B cell

After

immunization

Plasma

Cell

PC

Germinal

Center

T

B

B

B

T

B Cell

Structure of a Follicle

hypermutation

affinity maturation

class switch

antigen binding and processing

Ag

B cell binds antigen

Ag internalization and processing

Cell death

Antigen Binding and Processing

CD40

mIgM

MHC

Class II

B cell

resting t cell

CD28

Resting T Cell

T Cell

Receptor

T cell

priming of t cell cd40l

activated

antigen

presenting

cell-

B cell or

APC

other sig.

CD40L

Priming of T Cell-CD40L

CD28

T cell

t b collaboration cd80

viability

Germinal

Center

class switch

memory

CD40L

primed

T cell

IL-2

proliferation

CD28

CD80

T-B Collaboration-CD80

CD40

slide9

primed

T cell

CTLA4

CD28

primed

T cell

inhibition

Primed

B Cell

CTLA4

CD80

T-B Collaboration-CTLA4

CD28

Primed

B Cell

CD80

slide10

Blocking Agents

anti-CD40L

CD40L

B cell

T cell

CD28

CD80

CTLA4Ig

Collaboration blocked

? Anergy