Chapter 1: The Immune System
V(D)J recombination - Figure 7
Figure abbreviations: VDJ, variability, diversity and joining.
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 variable (V) and joining (J) segment genes. (Fig 1.7)
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 naïve B-cell surface of a unique Ig with Ag specificity: the B-cell receptor (BCR).
Germinal centre - Figure 8
Source: Levy N., Professor at Dartmouth College (link correct at time of publication; June 2015)
Naïve B cells exit the BM and circulate between blood, LNs and secondary lymphoid tissue in search of an Ag that will match the randomly determined BCR.
When naïve B cells encounter an Ag 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 (APCs), initiates Ag-dependent GC reaction.
In the peripheral dark zone of the GC, rapidly dividing B cells (centroblasts [CBs]) introduce random mutations in the H and L chains (somatic hypermutation). (Fig 1.8)
Somatic hypermutation and class-switch recombination - Figure 9
Figure abbreviations: CSR, class-switch recombination; FDC, follicular dendritic cell; SHM, somatic hypermutation.
Source: Klein U, et al. Nat Rev Immunol 2008; 8:22 -33
In the central light zone, CBs mature to centrocytes (CCs) and are selected for affinity with the help of T-follicular helper cells and dendritic cells. (Fig 1.9)
High-affinity CCs mature to either plasma cells or memory B cells and leave the GC. They may undergo Ig class switching 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 Ig specificity derived?
- What is meant by 'somatic hypermutation'?
