Complement Receptor Type 1 Suppresses Human B Cell Functions in SLE Patients

Kremlitzka, Mariann; Mácsik-Valent, Bernadett; Polgar, A. A.; Kiss, Emese; Poór, Gyula; Erdei, Anna

doi:10.1155/2016/5758192

Cited by 15 publications

(27 citation statements)

References 28 publications

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“…Whereas the role of human CR2 in B-cell activation is relatively well-established, much less is known about the exact function of CR1 (CD35). In contrast to CR2, CR1 has been described to mediate inhibitory signals ( 157 – 159 ). CR1 ligands include aggregated C3 and aggregated C3(H 2 O), which in contrast do not bind to CR2.…”

Section: Complement and Adaptive Immunitymentioning

confidence: 99%

Complement After Trauma: Suturing Innate and Adaptive Immunity

2018

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The overpowering effect of trauma on the immune system is undisputed. Severe trauma is characterized by systemic cytokine generation, activation and dysregulation of systemic inflammatory response complementopathy and coagulopathy, has been immensely instrumental in understanding the underlying mechanisms of the innate immune system during systemic inflammation. The compartmentalized functions of the innate and adaptive immune systems are being gradually recognized as an overlapping, interactive and dynamic system of responsive elements. Nonetheless the current knowledge of the complement cascade and its interaction with adaptive immune response mediators and cells, including T- and B-cells, is limited. In this review, we discuss what is known about the bridging effects of the complement system on the adaptive immune system and which unexplored areas could be crucial in understanding how the complement and adaptive immune systems interact following trauma.

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Section: Complement and Adaptive Immunitymentioning

confidence: 99%

Complement After Trauma: Suturing Innate and Adaptive Immunity

2018

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“…Having stressed the potential importance of this novel mechanism, we also understand that the causes of anti-nuclear autoantibodies and SLE disease are complex and are not explained by single mechanisms. For example, because C1s is effectively activated after C1 incubation with the nucleoli, it is also expected to cleave C4 and cause C4b deposition on the nucleoli to trigger C4b-mediated clearance and B cell tolerance (13,43,44).…”

Section: Discussionmentioning

confidence: 99%

“…Because apoptotic bodies are known to accumulate in SLE patients and, in mice, injection of dead cells causes antinuclear autoimmunity (11,13,41,42), the clearance functions of C1q and C4 are clearly relevant to SLE pathogenesis. However, other mechanisms may also be important by which these complement proteins increase host tolerance to autologous nuclear Ags, for example, C1q regulation of dendritic cells (DCs) and C4mediated B cell inhibition or tolerance (13,(43)(44)(45)(46). How C1r/C1s deficiency causes SLE has been mainly intuited based on studies of C1q and C4 (28,47).…”

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confidence: 99%

Broad Susceptibility of Nucleolar Proteins and Autoantigens to Complement C1 Protease Degradation

Cai

Wee

Chen

et al. 2017

The Journal of Immunology

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Anti-nuclear autoantibodies, which frequently target the nucleoli, are pathogenic hallmarks of systemic lupus erythematosus (SLE). Although the causes of these Abs remain broad and ill-defined, a genetic deficiency in C1 complex (C1qC1rC1s) or C4 is able to induce these Abs. Considering a recent finding that, in dead cells, nucleoli were targeted by C1q and two nucleolar autoantigens were degraded by C1r/C1s proteases, we considered that C1 could help protect against antinuclear autoimmunity by broadly degrading nucleolar proteins or autoantigens. Nucleoli were isolated to homogeneity and structurally defined. After C1 treatment, cleaved nucleolar proteins were identified by proteomic two-dimensional fluorescence difference gel electrophoresis and mass spectrometry, and further verified by Western blotting using specific Abs. The extent of nucleolar autoantigen degradation upon C1 treatment was estimated using SLE patient autoantibodies. The isolated nucleoli were broadly reactive with SLE patient autoantibodies. These nucleoli lacked significant autoproteolysis, but many nucleolar proteins and autoantigens were degraded by C1 proteases; >20 nucleolar proteins were identified as C1 cleavable. These were further validated by Western blotting using specific Abs. The broad autoantigenicity of the nucleoli may attribute to their poor autoproteolysis, causing autologous immune stimulation upon necrotic exposure. However, C1q targets at these nucleoli to cause C1 protease activation and the cleavage of many nucleolar proteins or autoantigens. This may represent one important surveillance mechanism against antinuclear autoimmunity because C1 genetic deficiency causes anti-nuclear autoantibodies and SLE disease.

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“…In the germinal centers, C3 degradation fragment‐coated immune complexes are recognized and retained by follicular DCs, enhancing the differentiation of memory and effector B cells . Regulators of complement also limit over‐reaction of the immune system, thus reducing inflammation, but nevertheless allow an antigen‐specific response by B cells . CR2, C4 binding protein, and CD46 modulate immunoglobulin class‐switching of B cells …”

Section: Interaction Between Complement and The Adaptive Immune Systemmentioning

confidence: 99%

“…60,61 Regulators of complement also limit over-reaction of the immune system, thus reducing inflammation, but nevertheless allow an antigen-specific response by B cells. 62,63 CR2, C4 binding protein, and CD46 modulate immunoglobulin class-switching of B cells. [64][65][66] Immune cell-derived complement plays a fundamental role in T-cell differentiation, activation, and expansion.…”

Section: Inter Ac Tion Bet Ween Complement and The Adaptive Immunementioning

confidence: 99%

The complex functioning of the complement system in xenotransplantation

Zhou

Hara

Cooper

2019

Xenotransplantation

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The role of complement in xenotransplantation is well-known, and is a topic that has been reviewed previously. However, our understanding of the immense complexity of its interaction with other constituents of the innate immune response and of the coagulation, adaptive immune, and inflammatory responses to a xenograft is steadily increasing. In addition, the complement system plays a function in metabolism and homeostasis. New reviews at intervals are therefore clearly warranted. The pathways of complement activation, the function of the complement system, and the interaction between complement and coagulation, inflammation, and the adaptive immune system in relation to xenotransplantation are reviewed. Through several different mechanisms, complement activation is a major factor in contributing to xenograft failure. In the organ-source pig, the detrimental influence of the complement system is seen during organ harvest and preservation, e.g., in ischemia-reperfusion injury. In the recipient, the effect of complement can be seen through its interaction with the immune, coagulation, and inflammatory responses. Genetic-engineering and other therapeutic methods by which the xenograft can be protected from the effects of complement activation are discussed. The review provides an updated source of reference to this increasingly complex subject.

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Complement Receptor Type 1 Suppresses Human B Cell Functions in SLE Patients

Cited by 15 publications

References 28 publications

Complement After Trauma: Suturing Innate and Adaptive Immunity

Complement After Trauma: Suturing Innate and Adaptive Immunity

Broad Susceptibility of Nucleolar Proteins and Autoantigens to Complement C1 Protease Degradation

The complex functioning of the complement system in xenotransplantation

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