11. B Cell Recognition and Response to Antigens

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11. B Cell Recognition and Response to Antigens
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TDAg
TIAg
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Stages of Humoral Immune Response
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11-1 B Cell Response to T Cell-Dependent Antigen
(TD)
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• Colocalization of T cells and B cells at the
  follicular border 2 days into the primary
  response.

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Nature Reviews Immunology 3, 962-972 (2003)
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1. B Cell Receptor Complex
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2. Activation of B cells
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Two-Signal Model of Humoral Immune Response
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• 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.

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Model of the role for lipid rafts in B-cell
activation
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B Cell Receptor Complex
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Activation of B Cells in Spleen
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Response Events in Germinal Center

• Affinity Maturation and the Generation of
  Memory B Cells

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Immune complexes bound to follicular dendritic
cells form iccosomes, which are released and can
be taken up by B cells in the germinal center
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Somatic hypermutation
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Nature Reviews Immunology 2, 688-698 (2002)
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Class Switching

• DNA rearrangement
• Antigen dependent
• Switch site
• Same VDJ
• TH cytokines

During B cell development, many B cells switch
from making one class of antibody to making
another, this process is called class switching.
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Antibody Class Switching
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Class switching in immunoglobulin heavy chain
genes
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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.

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Cellular interactions important for IgE
class-switch recombination
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Affinity
Strength of the reaction between a single
antigenic determinant and a single Ab combining
site
Affinity ? attractive and repulsive forces
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Avidity

• The overall strength of binding between an Ag
  with many determinants and multivalent Abs

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Affinity and avidity ???????
Ag1
Ag1
Ag1
Ag1




Ab1
Ab1
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• IgA plasma cells in green, IgG plasma cells
  in red. Lymph node

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• ?light chain in yellow,?light chain in red.
  Bone marrow

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Bone marrow is the home of plasma cells
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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

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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

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• B Cells Response to T Cell-Independent Antigens
  (TI Ag).
• LPS, Glycolipid, Nucleic acid.
• ? No memory and no MHC restriction.
• CD9B cell Response in Early Stage of
  Foot-and-Mouth Disease Virus Infection.

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CD5
CD9
CD5-
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11-2 B Cell Response to T Cell-Independent
Antigens (TI)
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Thymus-independent (TI)-1 antigens can activate B
cells without T-cell help
No Memory, no class switching
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11-3 Effector Mechanisms of Humoral Immune
Response
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Neutralization
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Opsonization
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Complement Activation
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