CD180 - CD180 molecule |Elisa - Clia - Antibody - Protein

Background

CD180, also known as RP105 (radioprotective 105 kDa protein), is a cell surface molecule prominently expressed on immune cells, particularly B cells, macrophages, and dendritic cells. As a member of the Toll-like receptor (TLR) family, CD180 plays a significant role in the immune system by recognizing microbial components and activating immune responses. Although structurally similar to TLRs, CD180 functions distinctly by forming complexes with other receptors rather than directly recognizing pathogen-associated molecular patterns (PAMPs). Its primary function is to regulate B cell activation, proliferation, and differentiation, which is crucial for antibody production and adaptive immunity. CD180 is a regulatory receptor that modulates the response of B cells to various antigens, providing an essential checkpoint in immune activation to avoid excessive immune responses and maintain balance.

Protein Structure

The CD180 protein has several structural features that facilitate its immune-regulatory role:

Extracellular Domain:

• CD180 has a leucine-rich repeat (LRR) domain in its extracellular region, characteristic of the TLR family. This domain is made up of repeated segments that create a horseshoe-like structure, allowing for protein-protein interactions. The LRR domain in CD180 does not directly bind to microbial molecules as seen in other TLRs but instead interacts with MD-1 (myeloid differentiation protein-1), which forms a complex with CD180 on the cell surface.
• The LRR domain’s specific structure in CD180 allows it to recognize and interact with certain ligands, regulating signal transduction in immune responses indirectly.

MD-1 Complex:

• CD180 is non-functional without the association with MD-1, which stabilizes its structure and facilitates cell surface expression. MD-1 is essential for the function of CD180, as it enables CD180 to transduce signals upon ligand binding and to play its role in immune cell regulation.

Transmembrane and Cytoplasmic Domains:

• Unlike other TLRs, CD180 lacks the Toll/Interleukin-1 receptor (TIR) domain typically found in the cytoplasmic region of TLRs. Instead, CD180 relies on associations with other signaling molecules to propagate downstream signaling.
• The absence of a TIR domain means that CD180 cannot independently transduce signals but needs to cooperate with other receptors to modulate immune responses.

Classification and Subtypes

CD180 belongs to the larger family of Toll-like receptors (TLRs), which are essential in recognizing and responding to microbial components in innate immunity. Within this family, CD180 is distinct because it requires the MD-1 molecule for function and lacks direct ligand recognition and signaling capabilities. It is grouped into a sub-class of TLR-like receptors with regulatory functions rather than direct pathogen recognition, differentiating it from classical TLRs that initiate inflammatory responses upon binding to specific ligands.

There are no significant functional subtypes of CD180, as the protein is conserved and shows little variation across different cell types or species. However, its expression levels may vary depending on cell type, immune status, and signaling context.

Function and Biological Significance

The function of CD180 centers around its role in regulating B cell responses and its involvement in controlling inflammatory reactions in immune cells. This modulation of immune responses is essential for balancing immunity and preventing inappropriate or excessive inflammation.

B Cell Regulation:

• CD180 plays a crucial role in B cell activation, differentiation, and proliferation. By interacting with MD-1 and forming complexes on B cells, CD180 can modulate the response of these cells to various stimuli, particularly in the presence of antigens or other immune activators. It is known to enhance B cell proliferation and support antibody production, which is crucial for effective adaptive immune responses.

Signal Transduction and Immune Activation:

• CD180 modulates immune activation indirectly through interactions with other TLRs and associated molecules, particularly in regulating responses to lipopolysaccharides (LPS) and other bacterial components. It does not directly recognize LPS but can modify the sensitivity of B cells and other immune cells to microbial products.
• The CD180-MD-1 complex also plays a role in limiting the pro-inflammatory responses induced by other TLRs, such as TLR4. This regulatory mechanism is important for preventing excessive inflammation that could lead to tissue damage or autoimmune reactions.

Role in Autoimmunity and Tolerance:

• CD180 is implicated in maintaining immune tolerance, particularly in its regulatory role in B cell function. Dysregulated CD180 expression or signaling has been linked to autoimmune diseases where immune tolerance to self-antigens is compromised, resulting in the activation of autoreactive B cells and subsequent autoimmune pathology.

Cell Survival and Differentiation:

• CD180 signaling supports cell survival in B cells, providing a co-stimulatory signal essential for B cell development. This function is particularly crucial during germinal center reactions, where B cells undergo rapid proliferation and differentiation.

Clinical Issues

CD180 expression and signaling have clinical implications, particularly in autoimmune diseases, chronic inflammation, and certain cancers:

Autoimmune Diseases:

• Alterations in CD180 expression have been associated with autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In SLE, B cell hyperactivity and loss of tolerance are observed, where abnormal CD180 signaling may contribute to the inappropriate activation of B cells against self-antigens. Understanding CD180’s role in these diseases could offer new therapeutic targets to restore immune tolerance and control autoimmune responses.

Chronic Inflammatory Diseases:

• CD180’s regulatory effect on TLR signaling pathways implies a potential role in chronic inflammatory conditions. Since CD180 can limit inflammatory responses, impaired CD180 function may result in prolonged and excessive inflammation, contributing to diseases such as inflammatory bowel disease (IBD) or chronic obstructive pulmonary disease (COPD).

Cancer:

• CD180 expression has been observed in certain hematologic cancers, such as B-cell lymphomas and chronic lymphocytic leukemia (CLL). Abnormal CD180 expression in these cancers may contribute to enhanced cell survival and resistance to apoptosis, promoting tumor growth. As a result, CD180 is being explored as a potential biomarker and therapeutic target in B cell malignancies.

Infectious Diseases:

• Given its role in modulating immune responses to microbial components, CD180 is a candidate for studying susceptibility to infections and responses to bacterial pathogens. It might influence susceptibility to infections by regulating B cell responses to bacterial products, potentially affecting how efficiently the immune system clears infections.

Summary

CD180, also known as RP105, is a member of the Toll-like receptor (TLR) family, specifically expressed on immune cells such as B cells, macrophages, and dendritic cells. Structurally, CD180 contains an extracellular leucine-rich repeat (LRR) domain but lacks the cytoplasmic TIR domain common to TLRs, preventing it from independently transducing signals. Instead, CD180 relies on forming a complex with MD-1, which stabilizes its structure and allows it to function as a regulatory molecule within the immune system.

CD180 is essential for regulating B cell activation, survival, and differentiation, which are critical for adaptive immune responses. Its function includes modulation of B cell responses, ensuring that B cells produce antibodies effectively while also maintaining immune tolerance to prevent autoimmunity. Clinically, dysregulated CD180 expression or signaling is linked to autoimmune diseases, chronic inflammatory conditions, and B cell malignancies. CD180’s regulatory role in immune responses and its contribution to immune homeostasis make it a potential target for therapeutic interventions in autoimmune diseases, cancers, and chronic inflammatory disorders. Understanding CD180’s precise mechanisms in immune modulation can further elucidate its potential in therapeutic strategies aiming to control immune responses and treat related pathologies.