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activation-induced cytidine deaminase (AID) - enzyme required for both SHM and isotype switching.
AID is expressed and active in non-GC proliferating B cells.
Follicular pathway leads to Bcl6-expressing germinal center B cells known as centroblasts and centrocytes.
Bcl6 is a transcriptional repressor that inhibits the diffenertiation towarrds plasmablasts by repressing Blimp1
Upon encounter with their cognate antigen, B cells rapidly upregulate CD69.
CD69 is an inhibitor the lymphoid egress , mediating receptor S1P1 and resulting in secondary lymphoid organ retention.
CXCR4 is expressed by plasmablasts. It is assumed that CXCR4 is responisble for residing of the plasmablasts in the extrafollicular foci.
Plasmablasts deficient in CXCR4 fail to migrate to normal sites of antibody.
EBI2 or GPR183 is highly expressed in B cells and is increased following their activation. EBI2 is required for the proper localization to inter- and outer-follicular niches of B cells following T-dependent antibody response.
EBI2 is downregulated when B cells differentiate into GC cells. Lack of EBI2 correlates with reduced T-dependent antibody response.
Differentiation between germinal center and extrafollicular-destined B cells occurs during this process of acivation through the expression of EBI2.
Loss of EBI2 --> GC incorporation
persistance of EBI2 receptor --> integration of activated B cell into EF pathway
ICOSL - inducible T-cell co-stimulator ligand, also known as ICOSLG
When GC competition proceeds without ICOSL, selection of high-affinity variants in otherwise normal GC reactions is impaired.
IL6, IL4 and BAFF are predominantly produced by innate immune cells and promote B cell differentiation into plasmablasts. Dysregulation of B cells may therefore be caused by the innate response.
Induction of high concentration of IRF4 after B cell activation drives the rapid generation of plasmablasts.
On the contrary, low concentrations of IRF4 may enable sustained expression of AID, CSR, and GC B cell response.
IRF8 dampens signaling via BCR and facilitates antigen-specific interaction with T helper cells. It also promotes antibody affinity maturation while antagonizing IRF4 driven differentiation of plasmablasts.
High IRF8:IRF4 ratio promotes GC differentiation.
PAX5 is a dual function activator and suppressor and is required for germinal center formation.
PAX5 along with Bach2 and Bcl6 stabilize The GC B cell state while antagonizing plasma cell differntiation.
ZEB2 is a transcription factor that is highly expressed in DN2 cells and aNAV cells. ZEB2 cooperatively acts with T-bet to promote effector differentiation and inhibit memory differentiation in cytotoxic T cells.
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CCR7 interacts with the chemokines CCL19 and CCL21
EBI2 is downregulated when B cells differentiate into GC cells. Lack of EBI2 correlates with reduced T-dependent antibody response. Differentiation between germinal center and extrafollicular-destined B cells occurs during this process of acivation through the expression of EBI2. Loss of EBI2 --> GC incorporation
persistance of EBI2 receptor --> integration of activated B cell into EF pathwayETS1 inhibits PC differentiation.
Deficiency of ETS1 may cause extrafollicular accumulation of autoreactive plasma cells.In vitro, it induces IFNγ and IL-21 in human T cells.
(IL12A)Annotated Interactions
No annotated interactions