The imperfect control of self-reactive germinal center B cells
R Brink - Current opinion in immunology, 2014 - Elsevier
Current opinion in immunology, 2014•Elsevier
Highlights•Many pathogenic autoantibodies have undergone somatic mutation and
selection in GCs.•Self-reactive GC B cells can be deleted if target self-antigen is present in
the GC.•Cross-reactive autoantibodies are most likely generated against organ-specific self-
antigens.•Anti-nuclear autoantibodies favoured when clearance of apoptotic GC cells is
compromised.Unlike T cells, B cells diversify their antigen receptor (BCR) binding
specificities at two distinct stages of differentiation. Thus, in addition to initial variable region …
selection in GCs.•Self-reactive GC B cells can be deleted if target self-antigen is present in
the GC.•Cross-reactive autoantibodies are most likely generated against organ-specific self-
antigens.•Anti-nuclear autoantibodies favoured when clearance of apoptotic GC cells is
compromised.Unlike T cells, B cells diversify their antigen receptor (BCR) binding
specificities at two distinct stages of differentiation. Thus, in addition to initial variable region …
Highlights
- Many pathogenic autoantibodies have undergone somatic mutation and selection in GCs.
- Self-reactive GC B cells can be deleted if target self-antigen is present in the GC.
- Cross-reactive autoantibodies are most likely generated against organ-specific self-antigens.
- Anti-nuclear autoantibodies favoured when clearance of apoptotic GC cells is compromised.
Unlike T cells, B cells diversify their antigen receptor (BCR) binding specificities at two distinct stages of differentiation. Thus, in addition to initial variable region gene rearrangements, B cells recruited into T-dependent immune responses further modify their BCR specificity via iterative rounds of somatic hypermutation (SHM) within germinal centers (GCs). Although critical for providing the high-affinity antibody specificities required for long-term immune protection, SHM can also generate self-reactive B cells capable of differentiating into autoantibody-producing plasma cells. Recent data confirm that self-reactive GC B cells can be effectively removed from the secondary repertoire so as to maintain self-tolerance. However, they can also escape deletion under certain circumstances and so contribute to autoimmune disease via production of somatically mutated, pathogenic autoantibodies.
Elsevier