Chapter 1: The Immune System
Source: Talk Design Page on "Evolving Immunity" by Matt Inlay. (link correct at time of publication; June 2015)
In B-cells the variable regions of the Ig L chains are encoded by the random joining of one of many variables (V) and joining (J) segment genes.
In addition to the above, for the H chain gene, a diversity (D) gene must also be rearranged.
The result of this random process is the expression on any individual naive B-cell surface of a unique Ig with Ag specificity: the B-cell receptor (BCR).
Source: Levy N., Professor at Dartmouth College (link correct at time of publication; June 2015)
Naive B-cells exit the BM and circulate between blood, LN, and secondary lymphoid tissue in search of an Ag that will match the randomly determined BCR.
When naive B-cells encounter an antigen within the germinal centre (GC) of a LN they undergo further variation and selection.
Binding of an Ag to the BCR, with the help of T-cells and antigen-presenting cells (APC), initiates Ag-dependent germinal centre reaction.
In the peripheral dark zone of the GC, rapidly dividing B-cells (centroblasts, CB) introduce random mutations in the H and L chains (somatic hypermutation).
Source: Klein U, et al. Nat Rev Immunol 2008; 8:22 -33
In the central light zone, CBs mature to centrocytes (CC) and are selected for affinity with the help of follicular helper T-cells and dendritic cells.
High-affinity CC mature to either plasma cells or memory B-cells and leave the GC. They may undergo Ig class switch by changing the Ig H chain.
Revision Questions
- What are the phases of B-cell development and where do they take place?
- How is the diversity of immunoglobulin specificity derived?
- What is meant by “somatic hypermutation”?
