Extrafollicular and follicular B cell activation by SARS-CoV-2 (Homo sapiens)
From WikiPathways
Description
The pathway model depicts the initial B cell activation inside the lymph node and the following activation routes to differentiate to either plasmablast cells following the extrafollicular pathway or memory B cells through the follicular pathway. Detailed pathway description and its application for data visualization can be found in this preprint doi: https://doi.org/10.1101/2022.12.19.521064
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Ontology Terms
Bibliography
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History
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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
AID | Protein | Q9GZX7 (Uniprot-TrEMBL) | activation-induced cytidine deaminase (AID) - enzyme required for both SHM and isotype switching. AID is expressed and active in non-GC proliferating B cells. |
APRIL | GeneProduct | ENSG00000161955 (Ensembl) | TNFSF13/APRILstimulates AID induction independently of CD40. |
Antibody diversification | Pathway | ||
BACH2 | GeneProduct | ENSG00000112182 (Ensembl) | Stabilizes GC B cells while aantagonizing plasma cell differeentiation. |
BAFF | GeneProduct | Q9Y275 (Uniprot-TrEMBL) | B cell activating factor (BAFF) |
BCL6 | GeneProduct | ENSG00000113916 (Ensembl) | 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 |
BCR | GeneProduct | ENSG00000186716 (Ensembl) | |
BLNK | GeneProduct | ENSG00000095585 (Ensembl) | |
BTLA | Protein | Q7Z6A9 (Uniprot-TrEMBL) | |
Blimp1 | GeneProduct | ENSG00000057657 (Ensembl) | PRDM1/Blimp-1 (B lymphocyte-induced maturation protein-1): Upregulation of Blimp-1 expression is associated with plasmablast differentiation. |
CCL19 | GeneProduct | ENSG00000172724 (Ensembl) | |
CCL21 | GeneProduct | ENSG00000137077 (Ensembl) | |
CCR7 | GeneProduct | ENSG00000126353 (Ensembl) | Increased expression of the CCR7 receptor indicates the interaction of B cells with the antigens.
CCR7 interacts with the chemokines CCL19 and CCL21 |
CD11c | GeneProduct | ENSG00000140678 (Ensembl) | DCs in the medullary cords or the T zone of the lymph nodes express high amounts of CD11c. CD11c forms a heterodimer with CD18 |
CD18 | GeneProduct | ENSG00000160255 (Ensembl) | |
CD19 | GeneProduct | ENSG00000177455 (Ensembl) | |
CD1d | Protein | P15813 (Uniprot-TrEMBL) | Antigen-presenting glycoprotein CD1d |
CD21 | GeneProduct | ENSG00000117322 (Ensembl) | CR2 or CD21 |
CD22 | GeneProduct | ENSG00000012124 (Ensembl) | |
CD35 | GeneProduct | ENSG00000203710 (Ensembl) | CD35 or CR1 |
CD40 | GeneProduct | ENSG00000101017 (Ensembl) | |
CD40L | Protein | P29965 (Uniprot-TrEMBL) | |
CD69 | GeneProduct | ENSG00000110848 (Ensembl) | 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. |
CD79A | GeneProduct | ENSG00000105369 (Ensembl) | |
CD80 | GeneProduct | ENSG00000121594 (Ensembl) | |
CD82 | GeneProduct | ENSG00000085117 (Ensembl) | |
CR1 | GeneProduct | ENSG00000203710 (Ensembl) | CR1 (CD35) |
CRP | GeneProduct | ENSG00000132693 (Ensembl) | C-reactive protein (CRP), an acute phase reactant in the IL-6 pathway commonly used as a biomarker of COVID-19 severity. |
CXCL12 | GeneProduct | ENSG00000107562 (Ensembl) | CXCL12 is expressed in the medullary cords of the lymph nodes and in the bone marrow. |
CXCL13 | Protein | O43927 (Uniprot-TrEMBL) | |
CXCR4 | GeneProduct | ENSG00000121966 (Ensembl) | 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. |
CXCR5 | GeneProduct | ENSG00000160683 (Ensembl) | |
Class Switch Recombination | Pathway | ||
Class Switch Recombination | Pathway | ||
Class switch recombination | Pathway | ||
Compl. C3 | Protein | P01024 (Uniprot-TrEMBL) | Complement C3 |
Compl. C4-A | Protein | P0C0L4 (Uniprot-TrEMBL) | |
EBI2 | GeneProduct | ENSG00000169508 (Ensembl) | 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 |
EBI3 | GeneProduct | ENSG00000105246 (Ensembl) | |
ETS1 | GeneProduct | ENSG00000134954 (Ensembl) | DN2 B cells and aNAV B cells express the lowest amounts of ETS1.
ETS1 inhibits PC differentiation. Deficiency of ETS1 may cause extrafollicular accumulation of autoreactive plasma cells. |
FOXO1 | GeneProduct | ENSG00000150907 (Ensembl) | Transcription factor FOXO1 inhibits T-bet-mediated effector functions and promotes memory CD8(+) T cell differentiation. |
FcRL5 | GeneProduct | ENSG00000143297 (Ensembl) | |
HSPA8 | GeneProduct | ENSG00000109971 (Ensembl) | associated with metabolic processes and autophagy |
ICOS | GeneProduct | ENSG00000163600 (Ensembl) | |
ICOSL | GeneProduct | ENSG00000160223 (Ensembl) | 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. |
IFIT2 | GeneProduct | ENSG00000119922 (Ensembl) | |
IFITM1 | GeneProduct | ENSG00000185885 (Ensembl) | |
IFN-α | Protein | P48551 (Uniprot-TrEMBL) | |
IFN-γ | Protein | P01579 (Uniprot-TrEMBL) | |
IFNG-AS1 | GeneProduct | ENSG00000255733 (Ensembl) | |
IGHV4-34 | GeneProduct | ENSG00000211956 (Ensembl) | |
IL-10 | GeneProduct | ENSG00000136634 (Ensembl) | |
IL-21 | Protein | Q9HBE4 (Uniprot-TrEMBL) | IL21 stimulates DN2 B cell differentiation into PCs. |
IL-2 | GeneProduct | ENSG00000109471 (Ensembl) | |
IL-4 | GeneProduct | ENSG00000113520 (Ensembl) | 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. |
IL-6 | GeneProduct | ENSG00000136244 (Ensembl) | IL-6 mainly promotes differentiation of antigen-specific B cells to plasmablasts. |
IL12 | GeneProduct | ENSG00000168811 (Ensembl) | IL-12 regulates humoral immunity by strongly inhibiting TFH differentiation.
In vitro, it induces IFNγ and IL-21 in human T cells. (IL12A) |
IL6 | Protein | Q75MH2 (Uniprot-TrEMBL) | |
IRF4 | GeneProduct | ENSG00000137265 (Ensembl) | 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 | GeneProduct | ENSG00000140968 (Ensembl) | 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. |
ISG15 | GeneProduct | ENSG00000187608 (Ensembl) | ISG15 acts as a chemoattractant for neutrophils. ISG15 is an autoimmune feature in autoimmune of memory-like B cells in SLE. |
IgG | Protein | P0DOX5 (Uniprot-TrEMBL) | |
IgG | Protein | P0DOX5 (Uniprot-TrEMBL) | |
IgM | Protein | P0DOX6 (Uniprot-TrEMBL) | |
IgM | Protein | P0DOX6 (Uniprot-TrEMBL) | |
MFGE8 | GeneProduct | ENSG00000140545 (Ensembl) | Mfge8 or FDC-M1 |
MHCII | Protein | ||
MS4A1 | GeneProduct | ENSG00000156738 (Ensembl) | MS4A1/CD20 |
NEAT1 | GeneProduct | ENSG00000245532 (Ensembl) | |
N | Protein | P0DTC9 (Uniprot-TrEMBL) | Nucleocapsid protein, N |
PAX5 | GeneProduct | ENSG00000196092 (Ensembl) | 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. |
PD1 | GeneProduct | ENSG00000188389 (Ensembl) | inhibitory receptor |
PRDM1 | GeneProduct | ENSG00000057657 (Ensembl) | |
PTCRA | GeneProduct | ENSG00000171611 (Ensembl) | Pre T-cell antigen receptor alpha, pT-alpha, pTa (pT-alpha-TCR) |
PTPRC | GeneProduct | ENSG00000081237 (Ensembl) | CD45 |
SAP | Protein | O60880 (Uniprot-TrEMBL) | |
SELL | GeneProduct | ENSG00000188404 (Ensembl) | homing receptor CD62L (SELL) |
SLAMF7 | GeneProduct | ENSG00000026751 (Ensembl) | |
S | Protein | P0DTC2 (Uniprot-TrEMBL) | Spike protein |
STAT5A | GeneProduct | ENSG00000126561 (Ensembl) | |
SYK | GeneProduct | ENSG00000165025 (Ensembl) | |
Somatic Hypermutation | Pathway | ||
TBET | GeneProduct | ENSG00000073861 (Ensembl) | TBX21/TBET is expressed in high amounts by DN2 B cells but also aNAV. |
TBX21 | Protein | Q9UL17 (Uniprot-TrEMBL) | T-bet expression influences TFH, as a lack of T-bet correlates with increased frequency of TFH |
TLR4 | GeneProduct | ENSG00000136869 (Ensembl) | |
TLR7 | GeneProduct | ENSG00000196664 (Ensembl) | |
TMSB10 | GeneProduct | ENSG00000034510 (Ensembl) | gene TMSB10 is Pax5-repressed |
TNF-α | Protein | P01375 (Uniprot-TrEMBL) | |
XBP1 | GeneProduct | ENSG00000100219 (Ensembl) | |
ZEB2 | GeneProduct | ENSG00000169554 (Ensembl) | 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. |
c-Maf | GeneProduct | O75444 (Uniprot-TrEMBL) | musculoaponeurotic fibrosarcoma (c-Maf) |
α-GalCer | Metabolite | 158021-47-7 (CAS) | α-galactosylceramide |
Annotated Interactions
No annotated interactions