11. B Cell Recognition and Response to Antigens 王 家 鑫王 家 鑫

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Stages of Humoral Immune Response

11-1 B Cell Response to T Cell-Dependent Antigen (TD)

Colocalization of T cells and B cells at the follicular border 2 days into the primary response.

Nature Reviews Immunology 3, (2003)

1. B Cell Receptor Complex

2. Activation of B cells

Two-Signal Model of Humoral Immune Response

Signals generated from the B-cell receptor and co-receptor synergize in B-cell activation. Binding of CR2 to C3d deposited on the surface of a pathogen cross-links the B-cell co-receptor complex with the B-cell receptor.

Model of the role for lipid rafts in B-cell activation

B Cell Receptor Complex

Activation of B Cells in Spleen

Response Events in Germinal Center — Affinity Maturation and the Generation of Memory B Cells

Immune complexes bound to follicular dendritic cells form iccosomes, which are released and can be taken up by B cells in the germinal center

Somatic hypermutation

Nature Reviews Immunology 2, (2002)

Class Switching DNA rearrangement –Antigen dependent –Switch site –Same VDJ –T H cytokines During B cell development, many B cells switch from making one class of antibody to making another, this process is called class switching.

Antibody Class Switching

Class switching in immunoglobulin heavy chain genes

Class Switching Recombination Class-switch recombination (CSR) of immunoglobulin heavy chains is the genetic process by which a B cell switches from the production of IgM to the production of IgG, IgE or IgA.

Cellular interactions important for IgE class-switch recombination

Affinity =  attractive and repulsive forces Ab Ag High Affinity Ab Ag Low Affinity Affinity Strength of the reaction between a single antigenic determinant and a single Ab combining site

Avidity The overall strength of binding between an Ag with many determinants and multivalent Abs K eq = 10 4 Affinity 10 6 Avidity 10

Ag1 Ab1 Ag1 Ab1 Affinity and avidity 亲和力与亲合力

IgA+ plasma cells in green, IgG+ plasma cells in red. Lymph node

λlight chain in yellow,κlight chain in red. Bone marrow

Bone marrow is the home of plasma cells

Summary Antigen-Induced Migration of B Cells and Helper T Cells Helper T Cell-Mediated Activation of B Cells: The Role of CD40-CD40L Interactions and Cytokines B Cell Differentiation into Antibody-Secreting Cells Heavy Chain Isotype (Class) Switching

2. Basic Features of Humoral Immune Response B Cell Subsets CD5+ B Cells→B1 Cells, TI Ag CD5- B Cells →B2 Cells, TD Ag CD9+ B Cells, TI Ag. No memory B Cells Response to T Cell-Dependent Antigens (TD Ag) Primary Humoral Immune Response Second Humoral Immune Response

B Cells Response to T Cell-Independent Antigens (TI Ag). LPS, Glycolipid, Nucleic acid. ★ No memory and no MHC restriction. CD9+B cell Response in Early Stage of Foot-and-Mouth Disease Virus Infection.

CD5+ CD9+ CD5-

11-2 B Cell Response to T Cell-Independent Antigens (TI)

Thymus- independent (TI)-1 antigens can activate B cells without T-cell help No Memory, no class switching

11-3 Effector Mechanisms of Humoral Immune Response

Neutralization

Opsonization Macrophage Extracellular bacteria Opsonization Ingestion by macrophage Digestion in lysosome

Complement Activation C2 C4 C1 Digestion in lysosome Bacteria in plasma C1 C4 C2 Complement activation Lysis and ingestion

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