Chap 25D - Infectious diseases

Describe B cells (naive and activated)

• Naïve B cells express both surface IgM and IgD as B cell receptors

• Most activated B cells differentiate into plasma cells that secrete IgM

Describe class switching (1st 2 steps)

1. Presence of an antigen leads to clonal selection of naïve B cells with B cell receptors specific to the antigen

2. Activated naïve B cells undergo clonal expansion -> form a large pool of B cells with identical receptors for the same antigen

Describe class switching (LAST steps)

• After stimulation from cytokines secreted by helper T cells, B cells may change the class (NOT the epitope specificity) of the antibodies they produce 

• Class switching occurs in individual B cell by further excision of DNA in the heavy chain gene cluster -> same VDJ segment to lie next to a different C gene

• Antibodies retains the same epitope specificity but with a different constant region

• The antibody isotype generated depends on the cytokines released by helper T cells that triggers the class switching

Describe purpose of class switching

• Allows more efficient humoral response 

• Eg. Defence against viruses and bacteria involves opsonisation with antibodies to facilitate phagocytosis by neutrophils and macrophages -> best mediated by IgG

Describe process of somatic mutation

• During clonal expansion, point mutations occur preferentially in the heavy chain VDJ gene segments and light chain VJ gene segments

• Requires cytidine deaminase, an enzyme that chemically modifies individual bases on the DNA

• Mutations occur at a rate 10⁶ times greater than spontaneous mutations in other genes

• Occurs in repeated cycles, each followed by antigen-driven clonal selection of B cells with antibodies of higher affinity

Describe outcome of somatic mutation

• Some mutations may increase the binding affinity of the antibody for its epitope

• B cells with these antibodies will be better able to bind to the antigen -> proliferate faster -> selected to differentiate into plasma cells and memory B cells

• Interaction of antibodies with a given epitope becomes tighter and more effective over time (affinity maturation) -> provides progressively better protection against the pathogen