BMOL30090 L8 B cells and Abs

watch YT video: slide 7

B cells

secrete Abs - many key roles in IR

vital for protection against many pathogens

antiserum

antiserum

Antibody cocktail

Ab isotypes image

Ab isotypes

IgA - mucosal surface (lung, gut, genitourinary), tend to be dimers

IgE - allergy, basophil activation

IgD - signal B cells to activate

IgM - produced earliest in Ab response

IgG - plasma cells: high affinity

IgA

mucosal surface (lung, gut, genitourinary), tend to be dimers

IgE

allergy, basophil activation

IgD

signal B cells to activate

IgM

produced earliest in Ab response

IgG

plasma cells - high affinity

Abs of different classes have distinct effector functions

overall Ab structure

tip of red is hypervariable region

all IgAs have same type of constant region, etc..

light chain in yellow

Ab diversity

• each individual has > 1 × 10¹¹ different Abs

• diversity at the variable region

• hypervariable region & framework regions

B cell variation

• similar to TCR genetic variation

• V(D)J recombination - any V D J can combine

• 2 types of light chains: lamda (120,000 possibilities), kappa (150,000 possibilities)

• total of 265 (? thousand) light chain combos

• total of 81,000 heavy chain combos

B cell variation - VDJ image

VDJ

• 200 different V genes

• 27 different D (Diversity) genes

• 15 different J (Joining) genes

combos of these contib to diversity

B cell development

As the B cell develops into a plasma cell, the B cell receptor gets secreted as an antibody with the exact same antigen specificity. (from google)

B cell receptor prods the same Ab that it reacts w/ the Ag of?

cellular level of B cell development image

B cell receptor image

Part 1. B cell activation

1. Ag binds to the B-cell receptor (BCR)

2. triggers a signal-transduction cascade

3. the BCR is internalised

4. Ag processed

5. newly synthesised MHC molecules & Ag peptides bound to the BCR form complexes

6. the peptide-MHC complexes are transported to cell surface

Part 1. B cell activation image

d: B cell receptor internalised

e: newly syn. MHC molecules & Ag peptides bound to BCR form complexes

Part 2. B cell activation

• peptide-MHC complexes are recognised by the T-cell receptor (TCR) of T-helper cells, leading to T-cell activation

• activated T-cells provide ‘help’ to the B cell, by both secreted cytokines (IL-4) and cell-cell interactions mediated by CD40 (B cell)-CD20L (T cell)

• leads to activation of B cells

Part 2. B cell activation image

T-B cooperation

activation of B cells by Ag involves signals from the BCR and T_FH cells or microbial Ags

reside in lymph nodes

pathway to B cell activation image

FDC - follicular dendritic cell

second phase of a primary B-cell IR

germinal centre: a B-cell nursery, nutrient rich, dense cell contact

all signals needed for intense cell proliferation

gene rearrangement and Ab maturation occurs here

plasma cells - leave via lymphatics

germinal centre image

human tonsillar germinal centre

• B cells found in the dark zone, light zone and mantle zone

• proliferating B cells = green

• rapidly proliferating B cells are present in the dark zone

• FDCs = red

• small recirculating B cells - in mantle zone

• large masses of CD4+ T cells are in the T cell zone = blue

tonsils

a type of lymph node

isotype switching

• naiive mature B cells prod both IgM and IgD

• encounter Ag → B cells proliferate & receive CD40 signal

• undergo Ab class switching to prod IgG, IgA or IgE Abs

• cytokine signals from T cells contrib to decision of which isotype

  • parasite infection: large amount of IL-4 = IgE

  • IFN-gamma: IgG

  • mucosal infection: IL-5 = IgA

affinity maturation by somatic hypermutation

• affinity maturation: process by which B cells respond to an Ag → Ab with better affinity

• acts randomly on rearranged V region genes

• clustered in the 3 hypervariable regions that make contact w/ the Ag

• activation induced cytidine deaminase (AID) introduces mutations into genes transcribed in B cells - somatic hypermutation

• (watch YT)

• if it encounters Ag, recognises it and activates B cell to change the sequence of V region (?)

• on nucleotide level

affinity maturation by somatic hypermutation image

primary vs secondary humoral responses

humoral response of covid infections image

secretory IgA at the epithelial surface

polymeric immunoglobulin receptor (pIgR) binds to the Fc regions of IgA and IgM

transports them across epithelial barriers

high affinity IgG and IgA Abs can neutralise toxins table

Fc receptors activate NK cells to destroy Ab-coated targets image

recap/summary