C3d

Background

The complement system is pivotal in identifying and eradicating pathogens, clearing physiological waste, orchestrating immune reactions, and maintaining homeostasis. Within this system, C3 is the most abundant component of serum and a key player in the innate immune response. C3d molecule is a cleaved fragment of C3 during complement activation, which has a molecular weight of approximately 35 kDa. When coupled with an antigen (Ag), C3d stimulates the immune system of organisms and enhances B-cell activity, thus possessing a function of immune adjuvant.

Its Gene ID: 718, UniProtKB ID: P01024, and OMIM ID: 120700.

Fig.1 Structure of Complement C3.^{1, 3}

C3d in Adaptive Immune Responses

Complement receptor 2 (CR2), a receptor for C3d, is primarily found on mature B cells and follicular dendritic cells (FDCs). The C3d-Ag complex can bind to both CR2 and immunoglobulin, thereby triggering C3d-mediated B-cell activation and significantly lowering the threshold for activation. The roles of C3d in the immune response are mainly as follows.

Fig.2 Functions of C3 in adaptive immune responses.^1,3

• C3d connects intrinsic and specific immunity. Through C3d-connected Ag targeting to CR2, it enhances Ag presentation and processing by all B cells and FDCs.
• C3d-Ag complex and immune complex (IC) can efficiently activate Ag-specific B cells through cross-linking of the B cell receptor (BCR) and CR2. Meanwhile, this activation leads to isotype switching in the case of T-cell-independent Ag.
• C3d-Ag complex can also be captured by FDCs in the spleen via CR2. In contrast to B cells, this labeled Ag can maintain its binding state to the cell surface for more extended periods. FDCs express three different C3 receptors that maintain FDCs binding and mediate IC for subsequent activation of Ag-specific B cells. In addition, the surface-bound C3d-Ag complexes of FDC can sustain Ag delivery, thereby participating in the generation and preservation of memory B cells.
• C3d-Ag complex can prolong the duration of Ag in vivo, thus enabling immunostimulation.
• C3d not only impacts humoral immunity but also influences cellular immune responses, as demonstrated by its interaction with a C3d receptor on murine Th1-type T cells.
• Depending on the receptor type it binds to, C3d can exert immunosuppressive effects, such as inhibiting B cell proliferation through CD35 binding and promoting the production of immunosuppressive factors like IL-10 and TGF-B through CR3 binding.

Immune Escape Mechanisms Targeting C3d

C3d is integral to the elicitation and regulation of immune responses. Its binding can impede key events in complement signaling cascades, potentially enabling cancer cells and foreign pathogens to evade immune surveillance. This interference can occur through the blockade of C3d binding sites, leading to complement inactivation, or by deliberately binding with C3d to approach host cells. For instance, membrane-binding proteases and enhanced expression of complement inhibitors can shield them from complement-induced destruction. In addition, yeast can exploit complement-binding proteins to bind C3d, facilitating their access to new host cells expressing CR2.

As a leading global supplier of antibodies, Creative Biolabs offers our customers a variety of anti-C3d antibody products that are suitable for 6 different applications, including WB, IHC, FC, etc. Additionally, we provide ELISA assay kits for C3d and natural protein to meet your various research needs.

C3d Functional Service

Creative Biolabs presents a comprehensive selection of C3d-targeted products, including bespoke C3d-specific antibodies, ELISA kits for C3d detection, and C3d proteins. These expertly crafted reagents are essential for unraveling the interactions between C3d proteins and diverse molecular components, thereby facilitating research dedicated to devising therapeutic strategies across numerous diseases.

Fig.2 Deposition of C3d targets in human pathological conditions.^{2, 3}

Researchers have developed a promising approach to address challenges posed by complement-mediated diseases treated with systemic inhibitors. To address these challenges, scientists created fusion proteins by combining factor H, with a monoclonal antibody targeting C3d. C3d’s deposition at active complement sites allows targeted localization, minimizing systemic effects, which can be detecting by immunostaining assay. In mouse and rat injury models, this strategy achieved over 75% tissue complement inhibition while avoiding systemic complement blockade, offering a potential pathway to safer therapeutic interventions.

Creative Biolabs provides a comprehensive suite of C3d-centric services, including assays for C3d binding and customized functional assessments. These offerings are carefully crafted to aid distinguished clients in progressing their clinical and research endeavors.

References

1. Erdei, Anna, et al. "New aspects in the regulation of human B cell functions by complement receptors CR1, CR2, CR3 and CR4." Immunology Letters 237 (2021): 42-57.
2. Liu, Fei, et al. "C3d-Targeted factor H inhibits tissue complement in disease models and reduces glomerular injury without affecting circulating complement." Molecular Therapy 32.4 (2024): 1061-1079.
3. Distributed under Open Access license CC BY 4.0, without modification.