BST1

Official Full Name

bone marrow stromal cell antigen 1

Organism

Homo sapiens

GeneID

683

Background

Bone marrow stromal cell antigen-1 is a stromal cell line-derived glycosylphosphatidylinositol-anchored molecule that facilitates pre-B-cell growth. The deduced amino acid sequence exhibits 33% similarity with CD38. BST1 expression is enhanced in bone marrow stromal cell lines derived from patients with rheumatoid arthritis. The polyclonal B-cell abnormalities in rheumatoid arthritis may be, at least in part, attributed to BST1 overexpression in the stromal cell population. [provided by RefSeq, Jul 2008]

Synonyms

CD157; cADPR2;

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Detailed Information

The BST1 gene, also known as Bone Marrow Stromal Cell Antigen-1 or CD157, is located on human chromosome 4p15.32. It encodes a glycosylphosphatidylinositol (GPI)-anchored type II transmembrane protein. Structurally, BST1 shares significant similarity with CD38, with both proteins belonging to the ADP-ribosyl cyclase family. Specifically, the amino acid sequence of BST1 exhibits approximately 33% similarity to CD38, suggesting potential functional overlap or cooperation. BST1 was initially identified and cloned from bone marrow stromal cell lines derived from patients with rheumatoid arthritis, which is reflected in its naming. Its expression is not ubiquitous but is selectively observed in certain cell types and tissues, most prominently in bone marrow stromal cells, as well as in various immune cells and some non-hematopoietic tissues. The GPI-anchored nature of BST1 means that it is not directly embedded in the plasma membrane but instead "hangs" on the outer membrane surface via the GPI structure, a feature critical for its functional role and intercellular interactions. This anchoring may enable BST1 to localize to specific membrane microdomains or to be released enzymatically in a soluble form to exert biological effects.

Biological Significance

The primary biological function of BST1 centers on its enzymatic activity, catalyzing two interconnected biochemical reactions. First, it converts β-nicotinamide adenine dinucleotide (β-NAD⁺) into cyclic ADP-ribose (cADPR). Second, it hydrolyzes cADPR to generate ADP-ribose. cADPR is widely recognized as a crucial intracellular second messenger, primarily involved in mobilizing intracellular calcium. By acting on ryanodine receptor-sensitive endoplasmic reticulum calcium stores, cADPR facilitates calcium release into the cytoplasm, triggering a variety of calcium-dependent cellular processes, including gene expression regulation, cell proliferation, differentiation, and cytokine secretion. Therefore, BST1 indirectly functions as a "regulatory valve" for intracellular calcium signaling by modulating cADPR levels.

Figure 1. Schematic representation of BST1-mediated intracellular signaling. (Ortolan E, et al., 2019)

Within the immune system, BST1 plays a particularly critical role. As its name implies, BST1 is highly expressed in bone marrow stromal cells, which form a central component of the microenvironment for B cell development and differentiation. Studies indicate that BST1 promotes the growth of pre-B cells, likely through cADPR-mediated regulation of intracellular calcium signaling, providing essential positive cues for early B cell development. This underscores BST1's indispensable role in the early establishment of adaptive immunity, particularly humoral immunity. However, BST1 function is context-dependent. In autoimmune diseases such as rheumatoid arthritis, aberrantly elevated expression of BST1 in stromal cells has been observed. Such overexpression may lead to excessive local cADPR levels, disrupting the homeostasis of the pre-B cell microenvironment, promoting abnormal polyclonal B cell activation and proliferation, and contributing to autoantibody production and disease progression. Beyond the bone marrow, BST1 is also expressed in myeloid cells, including monocytes and macrophages, where it may regulate inflammatory responses and functional states, participating in innate immune responses. Recent genome-wide association studies have further linked polymorphisms at the BST1 locus with Parkinson's disease risk, extending its functional relevance to the nervous system. While the precise mechanisms remain to be fully elucidated, potential pathways include BST1-mediated calcium signaling dysregulation, modulation of neuroinflammation, or microglial dysfunction, offering new perspectives on the immunological mechanisms underlying neurodegenerative diseases.

Clinical Relevance

The clinical significance of BST1 primarily lies in its potential as a disease biomarker and therapeutic target. In autoimmune disorders, especially rheumatoid arthritis, BST1 expression correlates with disease activity, making it an attractive research indicator. Assessing BST1 expression in synovial tissue or specific peripheral blood cell subsets may aid in more precise disease stratification or prognostic evaluation. More importantly, given BST1's role in promoting pathological B cell proliferation and antibody production, inhibitors targeting BST1 could theoretically interfere with these processes, offering novel therapeutic approaches for RA. However, due to its high structural and functional similarity with CD38-widely expressed across immune cells and functionally well-characterized-current drug development within this family (e.g., the anti-CD38 monoclonal antibody daratumumab for multiple myeloma) primarily focuses on CD38. Developing BST1-specific therapeutics without affecting CD38 function remains a translational challenge.

In neurodegenerative diseases, the strong association between BST1 and genetic susceptibility to Parkinson's disease positions it as a key gene for understanding PD pathophysiology. Although no BST1-targeted therapies have yet reached clinical application, this discovery has accelerated research into the role of immune and inflammatory pathways in PD. Investigating how BST1 variants affect microglial activity, α-synuclein aggregation and clearance, and subsequent dopaminergic neuron loss represents a cutting-edge focus in neuroscience. Future breakthroughs may lead to strategies that modulate BST1 pathways to slow or treat PD. Additionally, as a GPI-anchored protein, BST1 may shed into the circulation, offering potential as a detectable liquid biomarker for noninvasive PD diagnosis or disease monitoring. Overall, as a multifunctional molecule bridging immune and nervous system biology, the clinical utility of BST1 requires further elucidation through precise characterization of its cell type-specific functions and downstream signaling pathways.

References

Kaisho T, Ishikawa J, Oritani K, et al. BST-1, a surface molecule of bone marrow stromal cell lines that facilitates pre-B-cell growth. Proc Natl Acad Sci U S A. 1994;91(12):5325-5329.
Chosa N, Ishisaki A. Two novel mechanisms for maintenance of stemness in mesenchymal stem cells: SCRG1/BST1 axis and cell-cell adhesion through N-cadherin. Jpn Dent Sci Rev. 2018 Feb;54(1):37-44.
Ortolan E, Augeri S, Fissolo G, Musso I, Funaro A. CD157: From immunoregulatory protein to potential therapeutic target. Immunol Lett. 2019 Jan;205:59-64.

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