BLK Antibody

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Description

Introduction

The BLK Antibody is a critical research tool for studying the B lymphocyte kinase (BLK), a non-receptor tyrosine kinase expressed predominantly in B cells and certain T cell subsets . BLK plays a pivotal role in B-cell receptor (BCR) signaling, autoimmune regulation, and marginal zone (MZ) B-cell development . This antibody is widely used in immunological research to detect BLK protein expression via Western blot (WB), immunoprecipitation (IP), and flow cytometry .

Structure and Function of BLK Antibody

BLK antibodies are designed to target the 55–58 kDa BLK protein, which contains a Src-homology 3 (SH3) domain, a kinase domain, and a unique region (UR) critical for signaling . Commercially available antibodies, such as those from Cell Signaling Technology (CST) and Affinity Biosciences, are validated for specificity to endogenous BLK in human and murine models .

Antibody SourceReactivityApplicationsMolecular Weight
CST #3262HumanWB55 kDa
CST #66002HumanWB55 kDa
Affinity BiosciencesHumanELISA, WB, IHC58 kDa

Autoimmune Disease Studies

BLK antibodies have been instrumental in linking BLK dysregulation to autoimmune conditions like rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) . A cis-regulatory haplotype associated with reduced BLK expression in early B cells correlates with increased autoimmune risk .

B-Cell Signaling Pathways

BLK interacts with BANK1 and PLCγ2 to modulate BCR signaling. Silencing BLK reduces BANK1-PLCγ2 complex formation, highlighting its role in signal transduction . Antibodies have confirmed BLK’s negative regulatory effects on B-cell activation thresholds .

Marginal Zone (MZ) B-Cell Development

Studies using BLK antibodies revealed that BLK-deficient mice exhibit impaired MZ B-cell development but enhanced humoral responses to T-independent antigens . This underscores BLK’s dual role in B-cell homeostasis and activation .

Autoimmune Disease Mechanisms

  • Reduced BLK expression in early B cells correlates with autoimmune susceptibility .

  • BLK haploinsufficiency enhances B-cell activation thresholds, contributing to hyperresponsiveness .

B-Cell Subsets

  • MZ B cells: High BLK expression is critical for their development and function .

  • FO B cells: Lower BLK levels suggest subset-specific regulatory roles .

Cross-Species Conservation

BLK antibodies are effective in murine models, enabling comparative studies of B-cell signaling .

Challenges and Future Directions

  • Specificity Issues: Early commercial antibodies exhibited cross-reactivity with other Src kinases (e.g., Lyn, Fyn) .

  • Emerging Tools: Development of isoform-specific antibodies could refine studies of BLK’s role in autoimmune vs. infectious contexts .

Product Specs

Buffer
PBS with 0.1% Sodium Azide, 50% Glycerol, pH 7.3. Store at -20°C. Avoid freeze-thaw cycles.
Lead Time
Typically, we can ship your products within 1-3 business days after receiving your order. Delivery times may vary depending on the purchase method and location. Please consult your local distributors for specific delivery timelines.
Synonyms
B lymphocyte kinase antibody; B lymphoid tyrosine kinase antibody; Blk antibody; BLK nonreceptor tyrosine kinase antibody; BLK_HUMAN antibody; EC 2.7.10.2 antibody; MGC 10442 antibody; MGC10442 antibody; MODY 11 antibody; MODY11 antibody; P55 BLK antibody; p55-BLK antibody; Tyrosine kinase B lymphocyte specific antibody; Tyrosine protein kinase antibody; Tyrosine-protein kinase BLK antibody
Target Names
BLK
Uniprot No.

Target Background

Function
BLK, a non-receptor tyrosine kinase, plays a crucial role in B-lymphocyte development, differentiation, and signaling. B-cell receptor (BCR) signaling necessitates tight regulation of various protein tyrosine kinases and phosphatases, along with associated coreceptors. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling pathways leading to B-cell activation. BLK signaling is essential for transmitting signals through surface immunoglobulins, supporting the transition from pro-B to pre-B cells, and regulating signaling for growth arrest and apoptosis downstream of the B-cell receptor. Specifically, BLK binds to and phosphorylates CD79A at tyrosine residues 188 and 199, as well as CD79B at tyrosine residues 196 and 207. It also phosphorylates the immunoglobulin G receptors FCGR2A, FCGR2B, and FCGR2C. In collaboration with FYN and LYN, BLK plays a crucial role in pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation. Additionally, it contributes to BTK activation by indirectly stimulating BTK intramolecular autophosphorylation. In pancreatic islets, BLK acts as a modulator of beta-cell function by upregulating PDX1 and NKX6-1, thereby stimulating insulin secretion in response to glucose. BLK phosphorylates CGAS, promoting its retention in the cytosol.
Gene References Into Functions
  1. Our research indicated that the BLK rs13277113 polymorphism contributes to the genetic background of rheumatoid arthritis (RA) in the Chinese population. Notably, the association of BANK1 rs3733197 polymorphism with RA was dependent on the genotype of BLK rs13277113 polymorphism, highlighting the role of B-cell response in the pathogenesis of RA. PMID: 28925718
  2. This study suggests a novel association between specific TNFSF4 and BLK gene polymorphisms and allergic rhinitis risk. PMID: 28713926
  3. This meta-analysis confirms that polymorphisms in the BLK alleles rs13277113 A/G, rs2736340 T/C, and rs2248932 T/C are associated with susceptibility to systemic lupus erythematosus (SLE) in Caucasian and Asian populations. PMID: 27067206
  4. This meta-analysis confirms the association of rs548234/ATG5, rs2736340/BLK and rs10516487/BANK1 with systemic lupus erythematosus in Chinese Han, reinforcing our hypothesis of their epistatic effect in regulating B-cell signaling in SLE. PMID: 26420661
  5. Our study provides evidence that human BLK is a genuine proto-oncogene capable of inducing tumors. We demonstrate a novel BLK activity-dependent tumor model suitable for studying BLK-driven lymphomagenesis and screening for novel BLK inhibitors in vivo. PMID: 28670978
  6. The rs13277113 GA genotype of BLK is more prevalent in Systemic Lupus Erythematosus patients and may play a role in low gene expression and increased flares. PMID: 27864698
  7. This meta-analysis suggests that FAM167A-BLK rs2736340 polymorphism is associated with several autoimmune diseases. PMID: 27105348
  8. The SNPs in TNFSF4 and FAM167A-BLK may contribute to asthma and allergic rhinitis gene risk in the Han Chinese cohort. PMID: 27088737
  9. The systemic lupus erythematosus variant Ala71Thr of BLK significantly reduces protein abundance and binding to BANK1 by impairing the SH3 domain function. PMID: 26821283
  10. We report a novel BLK gene variant in common variable immunodeficiency patients that leads to suppressed B-cell proliferation and reduced ability of B-cells to elicit antigen-specific CD4(+) T-cell responses. PMID: 25926555
  11. A primary mechanism underlying the association of BLK with autoimmune disease involves lowered thresholds for basal B cell receptor signaling, enhanced B cell-T cell interactions, and altered patterns of isotype switching. PMID: 26246128
  12. Our study reveals a previously unappreciated role of reduced BLK expression on extraperitoneal accumulation of B1a cells in mice, as well as the presence of IgG autoantibodies and B1-like cells in humans. PMID: 25972485
  13. Our findings support previous observations that variants in the RHOB and FAM167A-BLK genes may be associated with susceptibility to systemic sclerosis. PMID: 25470816
  14. This study places Blk upstream of the p190RhoGAP-RhoA pathway in Galpha13-activated cells, overall representing an opposing signaling module during CXCL12-triggered invasion. PMID: 25025568
  15. This report highlights the role of BLK genetic variants in conferring risk of systemic lupus erythematosus in the Chinese population. PMID: 24091983
  16. The observations suggest that C8orf13-BLK, in combination with STAT4, plays a pivotal role in creating genetic susceptibility to polymyositis/dermatomyositis in Japanese individuals. PMID: 24632671
  17. B-lymphoid tyrosine kinase (Blk) is an oncogene and a potential target for therapy with dasatinib in cutaneous T-cell lymphoma. PMID: 24919804
  18. This study demonstrates that both lupus-associated functional variants contribute to the autoimmune disease association by modulating transcription of BLK in B cells, potentially altering immune responses. PMID: 24702955
  19. Our study provides the first evidence for epistasis between BLK and BANK1 in systemic lupus erythematosus from a Chinese population. PMID: 24085759
  20. The BLK region was significantly associated with Kawasaki disease susceptibility in populations of Korean and European descent. PMID: 24023612
  21. BANK1 and BLK play roles in B-cell signaling through phospholipase C gamma 2. PMID: 23555801
  22. SNPs in the FAM167A-BLK region, but not the BANK1 SNPs, were associated with the development of primary Sjogren's syndrome in Han Chinese. PMID: 23899688
  23. This study confirms BANK1 as an RA susceptibility gene and for the first time provides evidence for epistasis between BANK1 and BLK in RA. PMID: 23646104
  24. This study demonstrated that the loss-of-function BLK-p.A71T mutation is very unlikely to cause MODY; instead, it may modestly influence type 2 diabetes risk through an interaction with obesity. PMID: 23224494
  25. The functional SNP BLK rs2248932 T/C variant allele was associated with rheumatoid arthritis development. PMID: 22740142
  26. Blk allele expression differences at the protein level are restricted to early B cells. PMID: 22678060
  27. Genetic variants in the promoter region of BLK may cause dysregulation of BLK expression, which could contribute to the initiation and progression of systemic lupus erythematosus. PMID: 22313735
  28. BCR-ABL downregulates the Blk gene (encoding B-lymphoid kinase) through c-Myc in leukemic stem cells in chronic myeloid leukemia. PMID: 22797726
  29. Expression of RUNX1 isoforms and its target gene BLK in childhood acute lymphoblastic leukemia. PMID: 22748822
  30. Rare and common regulatory variants in BLK are involved in disease susceptibility in systemic lupus erythematosus. PMID: 22696686
  31. Single nucleotide polymorphism in the BLK gene is associated with Kawasaki disease. PMID: 22446961
  32. Allelic variation in Blk does not play a major role in determining multifocal motor neuropathy susceptibility. PMID: 22003931
  33. This study shows a genetic interaction between BANK1 and BLK, and demonstrates that these molecules interact physically. PMID: 21978998
  34. Moderate evidence exists for an association between the BLK rs13277113, rs2248932 variants and systemic lupus erythematosus. PMID: 21152986
  35. This study evaluated SNP rs2248932 from BLK and further defined its role in systemic lupus erythematosus (SLE) risk; its association with SLE was confirmed in the Chinese Han population. PMID: 20130895
  36. Studies have found that IRF5, STAT4, and BLK are associated not only with systemic lupus erythematosus but also rheumatoid arthritis and systemic sclerosis. [review] PMID: 20453440
  37. Our findings do not support a major implication of the C8orf13-BLK gene region in susceptibility to Giant cell arteritis. PMID: 20156505
  38. Results indicate that the FAM167A-BLK region may be a shared genetic factor for a number of autoimmune diseases in multiple populations, but the genetic contribution may be greater in Asian populations. PMID: 19740902
  39. This genetic polymorphism is associated with systemic sclerosis in North-American and European populations. PMID: 19796918
  40. Our findings indicate that the rs13277113A allele is associated not only with SLE but also with SSc and that the FAM167A-BLK region is a common genetic risk factor for both SLE and SSc. PMID: 20131239
  41. Transcription of the B cell-specific blk gene is regulated by NERF/ELF-2 and AML1. PMID: 14970218
  42. This study identified and confirmed through replication two new genetic loci for SLE: a promoter-region allele associated with reduced expression of BLK and increased expression of C8orf13 and variants in the ITGAM-ITGAX region. PMID: 18204098
  43. The association of the C8orf13-BLK region with systemic lupus erythematosus was replicated in a Japanese population. PMID: 19180478
  44. Our data confirmed the association of STAT4 (rs7574865, odds ratio (OR) =1.71, P=3.55 x 10(-23)) and BLK (rs13277113, OR=0.77, P=1.34 x 10(-5)) with SLE. PMID: 19225526
  45. Blk is constitutively tyrosine phosphorylated in malignant cutaneous T-cell lymphoma cell lines and spontaneously active in kinase assays. PMID: 19351960
  46. STAT4 and BLK displayed a strong genetic association with primary antiphospholipid syndrome. PMID: 19644876
  47. Findings point to BLK as a previously unrecognized modulator of beta-cell function, a deficit of which may lead to the development of diabetes. PMID: 19667185
  48. Observational study and genome-wide association study of gene-disease association and gene-gene interaction. (HuGE Navigator) PMID: 19503088

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Database Links

HGNC: 1057

OMIM: 191305

KEGG: hsa:640

STRING: 9606.ENSP00000259089

UniGene: Hs.146591

Involvement In Disease
Maturity-onset diabetes of the young 11 (MODY11)
Protein Families
Protein kinase superfamily, Tyr protein kinase family, SRC subfamily
Subcellular Location
Cell membrane; Lipid-anchor.
Tissue Specificity
Expressed in lymphatic organs, pancreatic islets, Leydig cells, striate ducts of salivary glands and hair follicles.

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