Chapter 11

B-Cell Generation, Activation, and Differentiation

本章大綱 :1. B-Cell Maturation

2. B-Cell Activation and Proliferation

3. The Humoral Response

4. In Vivo Studies for Induction of Humoral Response

5. Germinal Centers and Antigen-Induced B-Cell Differentiation

6. Regulation of B-Cell Development

7. Regulation of the Immune Effector Response

B-Cell Maturation

Overview of B-cell Development

Sites of B-cell maturation – before birth: yolk sac fetal liver fetal bone marrow after birth: bone marrow

Bone-Marrow Stromal Cells Are Required for Maturation of Progenitor B Cells into Precursor B Cells

Direct contact is required

Sequence of Events and Characteristics of the Stages in BCell Maturation in the Bone Marrow

Pre-B Cell Receptor

Heavy chain: Chain

Surrogate light chain: VpreB and 5

Ig/Ig

Sequential Expression of Membrane Ig and Surrogate Light Chain at Different Stages of

B-Cell Differentiation in the Bone Marrow

Experimental Evidence for Negative Selection of Self-Reactive B Cells During Maturation in the Bone Marrow

B-Cell Activation and Proliferation

Two Distinct Signals for B-Cell Activation

The Initial Stages of Signal Transduction by an Activated B-Cell Receptor (BCR)

Signal Transduction Pathways Activated by the BCR

BCR Complex: TAPA-1 (CD81), CD2 (CD21), and CD19

Sequence of Events in B-Cell Activation by a Thymus-Dependent Ag

Initial Contact between a T Cell and B Cell

a T-B Conjugate

Clonal Anergy in Mature Peripheral B Cells

Production of double-transgenic mice carrying transgenes encoding HEL and anti-HEL Ab:

FACS Analysis of Peripheral B Cells that Bind HEL Compared with Membrane IgM Level:

Clonal Deletion of Self-Reactive Mature Peripheral B Cells

Production of double-transgenic mice expressing the class I Kb molecule and anti-Kb Ab:

FACS analysis of bone marrow and peripheral (lymph node) B cells for Kb binding versus mIgM:

Concentration and Isotype of Serum Ab Following Primary (1° ) and Secondary (2 ° ) Immunization with Ag

Hapten-Primed and Carrier-Primed Cells Are Separate Populations

A Peripheral Lymph Node

Cellular Events within Secondary Follicles of Peripheral Lymph Nodes

The Frequency of Somatic Hypermutation Decreases with the Distance from the Rearranged V(D)J Gene

Interactions of Numerous Cytokines with B Cells Generate Signals Required for proliferation and Class Switching During the Differentiation of B Cells into Plasma Cells

The End

Clonal Anergy in Mature Peripheral B Cells