Entry
Name
B cell receptor signaling pathway - Homo sapiens (human)
Description
B cells are an important component of adaptive immunity. They produce and secrete millions of different antibody molecules, each of which recognizes a different (foreign) antigen. The B cell receptor (BCR) is an integral membrane protein complex that is composed of two immunoglobulin (Ig) heavy chains, two Ig light chains and two heterodimers of Ig-alpha and Ig-beta. After BCR ligation by antigen, three main protein tyrosine kinases (PTKs) -the SRC-family kinase LYN, SYK and the TEC-family kinase BTK- are activated. Phosphatidylinositol 3-kinase (PI3K) and phospholipase C-gamma 2 (PLC-gamma 2) are important downstream effectors of BCR signalling. This signalling ultimately results in the expression of immediate early genes that further activate the expression of other genes involved in B cell proliferation, differentiation and Ig production as well as other processes.
Class
Organismal Systems; Immune system
BRITE hierarchy
Pathway map
hsa04662 B cell receptor signaling pathway
Ortholog table
Network
Element
N00487 BCR-PLCG-Calcineurin signaling pathway
N01695 BCR-BCAP/CD19-PI3K signaling pathway
Drug
D06348 Yttrium Y 90 epratuzumab (USAN)
D06349 Yttrium Y 90 epratuzumab tetraxetan (USAN)
D08933 Inotuzumab ozogamicin (USAN/INN)
D09325 Blinatumomab (USAN/INN)
D09348 Fostamatinib disodium (USAN)
D09932 Moxetumomab pasudotox (USAN/INN)
D10560 Idelalisib (JAN/USAN/INN)
D10731 Spebrutinib besylate (USAN)
D10761 Polatuzumab vedotin (USAN)
D10893 Acalabrutinib (JAN/USAN/INN)
D11070 Tirabrutinib hydrochloride (JAN/USAN)
D11144 Axicabtagene ciloleucel (USAN)
D11231 Denintuzumab (USAN/INN)
D11232 Denintuzumab mafodotin (USAN/INN)
D11323 Umbralisib tosylate (USAN)
D11386 Tisagenlecleucel-T (USAN)
D11422 Zanubrutinib (JAN/USAN/INN)
D11428 Vecabrutinib (USAN/INN)
D11457 Fenebrutinib (USAN/INN)
D11502 Vecabrutinib succinate (USAN)
D11506 Parsaclisib hydrochloride (JAN/USAN)
D11720 Acalabrutinib maleate (USAN)
D11757 Inebilizumab (USAN/INN)
D11790 Mivavotinib citrate (USAN)
D11873 Rilzabrutinib (JAN/USAN/INN)
D11880 Brexucabtagene autoleucel (USAN)
D11990 Lisocabtagene maraleucel (USAN/INN)
D12050 Pirtobrutinib (JAN/USAN)
D12158 Elsubrutinib (USAN/INN)
D12160 Orelabrutinib (USAN/INN)
D12213 Tolebrutinib (JAN/USAN/INN)
D12285 Remibrutinib (JAN/USAN/INN)
D12383 Edralbrutinib (USAN/INN)
D12489 Atuzabrutinib (USAN/INN)
D12504 Nemtabrutinib (USAN/INN)
D12594 Tirabrutinib (USAN/INN)
D12704 Acalabrutinib maleate hydrate (JAN)
D12775 Polzastobart (USAN/INN)
D12954 Sovleplenib acetate (USAN)
Other DBs
Organism
Homo sapiens (human) [GN:
hsa ]
Gene
27071 DAPP1; dual adaptor of phosphotyrosine and 3-phosphoinositides 1 [KO:K12229 ]
10451 VAV3; vav guanine nucleotide exchange factor 3 [KO:K05730 ]
7409 VAV1; vav guanine nucleotide exchange factor 1 [KO:K05730 ]
7410 VAV2; vav guanine nucleotide exchange factor 2 [KO:K05730 ]
55024 BANK1; B cell scaffold protein with ankyrin repeats 1 [KO:K26239 ]
5534 PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268 ]
5535 PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268 ]
4772 NFATC1; nuclear factor of activated T cells 1 [KO:K04446 ]
4773 NFATC2; nuclear factor of activated T cells 2 [KO:K17332 ]
4775 NFATC3; nuclear factor of activated T cells 3 [KO:K17333 ]
2885 GRB2; growth factor receptor bound protein 2 [KO:K04364 ]
6654 SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099 ]
6655 SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099 ]
25780 RASGRP3; RAS guanyl releasing protein 3 [KO:K12362 ]
3265 HRAS; HRas proto-oncogene, GTPase [KO:K02833 ]
3845 KRAS; KRAS proto-oncogene, GTPase [KO:K07827 ]
4893 NRAS; NRAS proto-oncogene, GTPase [KO:K07828 ]
2353 FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379 ]
3725 JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448 ]
84433 CARD11; caspase recruitment domain family member 11 [KO:K07367 ]
8915 BCL10; BCL10 immune signaling adaptor [KO:K07368 ]
10892 MALT1; MALT1 paracaspase [KO:K07369 ] [EC:3.4.22.-]
1147 CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467 ] [EC:2.7.11.10 ]
8517 IKBKG; inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [KO:K07210 ]
4790 NFKB1; nuclear factor kappa B subunit 1 [KO:K02580 ]
5970 RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735 ]
8519 IFITM1; interferon induced transmembrane protein 1 [KO:K19831 ]
5295 PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
5296 PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
8503 PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
5290 PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922 ] [EC:2.7.1.153 ]
5293 PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922 ] [EC:2.7.1.153 ]
5291 PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922 ] [EC:2.7.1.153 ]
10288 LILRB2; leukocyte immunoglobulin like receptor B2 [KO:K06512 ]
10859 LILRB1; leukocyte immunoglobulin like receptor B1 [KO:K06512 ]
10990 LILRB5; leukocyte immunoglobulin like receptor B5 [KO:K06512 ]
11006 LILRB4; leukocyte immunoglobulin like receptor B4 [KO:K06512 ]
11024 LILRA1; leukocyte immunoglobulin like receptor A1 [KO:K06512 ]
11025 LILRB3; leukocyte immunoglobulin like receptor B3 [KO:K06512 ]
11026 LILRA3; leukocyte immunoglobulin like receptor A3 [KO:K06512 ]
11027 LILRA2; leukocyte immunoglobulin like receptor A2 [KO:K06512 ]
23547 LILRA4; leukocyte immunoglobulin like receptor A4 [KO:K06512 ]
79168 LILRA6; leukocyte immunoglobulin like receptor A6 [KO:K06512 ]
353514 LILRA5; leukocyte immunoglobulin like receptor A5 [KO:K06512 ]
102725035 leukocyte immunoglobulin-like receptor subfamily B member 3 [KO:K06512 ]
107987425 leukocyte immunoglobulin-like receptor subfamily B member 3 [KO:K06512 ]
107987462 leukocyte immunoglobulin-like receptor subfamily B member 3 [KO:K06512 ]
112268336 leukocyte immunoglobulin-like receptor subfamily B member 3 [KO:K06512 ]
112268337 leukocyte immunoglobulin-like receptor subfamily B member 3 [KO:K06512 ]
112268340 leukocyte immunoglobulin-like receptor subfamily B member 3 [KO:K06512 ]
107987441 leukocyte immunoglobulin-like receptor subfamily B member 3 [KO:K06512 ]
118788 PIK3AP1; phosphoinositide-3-kinase adaptor protein 1 [KO:K12230 ]
Compound
C01245 D-myo-Inositol 1,4,5-trisphosphate
C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference
Authors
Niiro H, Clark EA.
Title
Regulation of B-cell fate by antigen-receptor signals.
Journal
Reference
Authors
Kurosaki T.
Title
Genetic analysis of B cell antigen receptor signaling.
Journal
Reference
Authors
Nitschke L.
Title
The role of CD22 and other inhibitory co-receptors in B-cell activation.
Journal
Reference
Authors
Morgan BP, Marchbank KJ, Longhi MP, Harris CL, Gallimore AM.
Title
Complement: central to innate immunity and bridging to adaptive responses.
Journal
Reference
Authors
Kurosaki T.
Title
Regulation of B-cell signal transduction by adaptor proteins.
Journal
Reference
Authors
Nitschke L, Tsubata T.
Title
Molecular interactions regulate BCR signal inhibition by CD22 and CD72.
Journal
Reference
Authors
Jumaa H, Hendriks RW, Reth M.
Title
B cell signaling and tumorigenesis.
Journal
Reference
Authors
Rickert RC.
Title
Regulation of B lymphocyte activation by complement C3 and the B cell coreceptor complex.
Journal
Reference
Authors
Zouali M, Sarmay G
Title
B lymphocyte signaling pathways in systemic autoimmunity: implications for pathogenesis and treatment.
Journal
Reference
Authors
Chiles TC.
Title
Regulation and function of cyclin D2 in B lymphocyte subsets.
Journal
Reference
Authors
Allam A, Marshall AJ
Title
Role of the adaptor proteins Bam32, TAPP1 and TAPP2 in lymphocyte activation.
Journal
Reference
Authors
Gold MR
Title
To make antibodies or not: signaling by the B-cell antigen receptor.
Journal
Reference
Authors
Fu C, Turck CW, Kurosaki T, Chan AC
Title
BLNK: a central linker protein in B cell activation.
Journal
Reference
Authors
Okada T, Maeda A, Iwamatsu A, Gotoh K, Kurosaki T
Title
BCAP: the tyrosine kinase substrate that connects B cell receptor to phosphoinositide 3-kinase activation.
Journal
Reference
Authors
Shinohara H, Maeda S, Watarai H, Kurosaki T
Title
IkappaB kinase beta-induced phosphorylation of CARMA1 contributes to CARMA1 Bcl10 MALT1 complex formation in B cells.
Journal
Related pathway
hsa04610 Complement and coagulation cascades
hsa04810 Regulation of actin cytoskeleton
KO pathway