2. FOCISB T-B collaboration2018 Pillai.ppt - Compatibility ... · T-independent ANTIGENS...

Advanced Course in Basic & Clinical Immunology

February 20, 2018

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T-B collaboration

Shiv Pillai MD, PhDMassachusetts General Hospital

Harvard Medical School

SLOs - T and B cell zones

CCL19 and CCL21draw naïve T cells to T cell zones

CXCL 13 brings naive B cells to follicle

BAFF keeps B cells alive


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Copyright © 2011 by Saunders, an imprint of Elsevier Inc.Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7th edition. Copyright © 2011 by Saunders, an imprint o

Antigen Delivery to Follicular B cells

Multivalent Structures can be T-independent antigens


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HAPTENS

T-independent ANTIGENS

T-dependent ANTIGENS

Haptens, Antigens, Immunogens

• Haptens are small molecules or moieties. They are antigens but not immunogens

• All immunogens are antigens

• All antigens are not immunogens


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T-DEPENDENT ACTIVATION OF B CELLS


T-B cell Migration and Interactions


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B Cell Antigen Presentation to Helper T cells


Distinct B and T cell epitopes must be linked


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Y

Y

MHCclass II

(loaded)

TCR

T

B

CD4

CD40

gp 39/CD40L

BCR

activated

The BCR internalizes specific protein antigens forprocessing and presentation to activated T cells


Helper T cell Activation of B Cells (1)


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Helper T cell Activation of B Cells (2)


Events in T–Dependent Humoral Responses


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T Follicular Helper Cell Induction and Function


Germinal Centers in Lymphoid Organs


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B Cell Antigen Presentation to Helper T cells


Events in T–Dependent Humoral Responses

1

2

3


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Sequential T-B interactions in immunity

1. T B - Forms extrafollicular B cell focus

2. B T - Generates T follicular helper cells

3. T B - Selection of high affinity B cells in light zone by TFH cells


B Cell Selection in Germinal Centers


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Ig Heavy Chain Isotype Switching

, IgG4


T cell subsets and human isotype switching (evolving)

TFH2 - IgE and IgG4 (cells make IL-4 andare BATF positive)

TH2 cells- GATA-3+; NOT drivers of classswitching


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Heavy Chain Isotype Switching


Heavy Chain Isotype Switching


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Somatic Mutations in Ig V genes


An Overview of Affinity Maturation


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Activation Induced Cytidine Deaminase

Neuberger JEM, 2007

AID and Somatic Mutation


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Molecular Mechanism of Ig Class Switching - I


Molecular Mechanism of Ig Class Switching - II


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Terminal differentiation into plasma cells

Signals: BCR, CD40, Cytokines such as IL-21 and IL-6

IRF4 and BLIMP-1 induce the XBP-1 transcription factor, ER stress

signals control splicing of XBP-1

BAFF family receptor BCMA for survival of long-lived plasma cells in

Bone marrow

IRF-4Blimp-1XBP-1

Pax-5

Mature B cell GC B cell Plasma cell

Bcl-6

Distinct transcription factors characterize mature B cells,GC B cells and plasma cells


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BCMA is critical for the maintenance of long-lived plasma cells

Shapiro-Shelef and Calame, NRI 5, 230-242

Helper T cell

T cell response

Initial T-B interaction

DC

Activated B cells generally REQUIRED for CD4+ T cell memory

CD4+ T memory cells

B-T interactions between previously activated cells


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An overview of B cell activation

Quietly into the night…….

2. FOCISB T-B collaboration2018 Pillai.ppt - Compatibility ... · T-independent ANTIGENS...

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