Covalent binding of C3b to monoclonal antibodies selectively up‐regulates heavy chain epitope recognition by T cells

Santoro, Lyse; Drouet, Christian; Reboul, Anne; Mach, Jean‐Pierre; Colomb, Maurice G.

doi:10.1002/eji.1830240725

Cited by 20 publications

(5 citation statements)

References 53 publications

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“…The delayed endosomal proteolysis results in an improved peptide loading on MHC class II molecules and an increased stability of these molecules in the lysosomes [105]. Consistent with this observation is the finding that attachment of C3b to the heavy chain of murine IgG results in a 100-fold reduction in the amount of IgG required for human B cell lines to stimulate heavy chain-specific T cell clones, without enhancing antigen presentation to light chain-specific T cell clones [106]. It is noteworthy that CD21 may be able to promote antigen presentation in non-specific B cells, without assistance from BCR [107].…”

Section: The Role Of Cd19/cd21 In B Cell Developmentsupporting

confidence: 71%

The Role of Complement in Immune and Autoimmune Responses

Leslie

Marquart

Nielsen³

2005

Transfus Med Hemother

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For more than 30 years it has been known that complement plays a central role in the development of humoral immune responses. Today it is clear that complement influences a variety of B cell functions, including the uptake, processing and presentation of foreign and selfantigens, the production of specific antibodies as well as shaping of the B cell repertoire. A central role in the performance of these functions is played by the B cell signalling triad consisting of the B cell receptor for antigen (BCR), a complex consisting of the iC3b/C3d fragmentbinding complement type 2 receptor (CR2, CD21) and its signalling element, CD19, and the IgG-binding receptor, Fc?RIIb (CD32). Recent evidence suggests that complement, in addition to facilitating the uptake and presentation of antigen to T helper cells by antigen-presenting cells, also regulates T cell functions by promoting the production of the pro-inflammatory cytokines TNF-a and IFN-? on the one hand, and the differentiation of regulatory T cells producing IL-10 on the other. This review aims at describing the present status of our understanding of the mechanisms underlying complement regulation of acquired immunity and autoimmunity.

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Section: The Role Of Cd19/cd21 In B Cell Developmentsupporting

confidence: 71%

The Role of Complement in Immune and Autoimmune Responses

Leslie

Marquart

Nielsen³

2005

Transfus Med Hemother

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“…The delayed endosomal proteolysis results in an improved peptide loading on MHC class II molecules and an increased stability of these molecules in the lysosomes [95]. Consistent with this observation is the finding that attachment of C3b to the heavy chain of murine IgG results in a 100-fold reduction in the amount of IgG required for human B-cell lines to stimulate heavy chain-specific T-cell clones, without enhancing antigen presentation to light chainspecific T-cell clones [96]. It is noteworthy that CD21 may be able to promote antigen presentation in non-specific B cells, without assistance from BCR [97].…”

Section: Complement-mediated Promotion Of Antigen Processing and Pressupporting

confidence: 71%

Regulation of B-Cell Activation by Complement Receptors and Fc Receptors

Nielsen

Leslie

2005

Transfus Med Hemother

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In addition to producing autoantibodies, B cells act as critical antigen presenting cells in autoimmune disease. Tight regulation of B-cell activity is required to ensure humoral immunity against pathogens, on the one hand, and to avoid detrimental autoreactivity, on the other. Activation of B cells is mediated through cross-binding of the B-cell antigen receptor (BCR) and is greatly enhanced by co-engagement of complement receptor type 2 (CD21, CR2) and its signaling element, CD19. Feedback inhibition of B-cell activity is mediated by the binding of IgG antibodies to Fc?RIIB (CD32). The extent to which the individual receptors are engaged depends on the context in which antigen is encountered, be it as antigen alone, as complement-opsonized antigen, or as antigen complexed with IgM or IgG antibodies. Both over-expression of CD19 and deficiency of elements centrally involved in negative signaling, e.g. Fc?RIIB and Lyn, lead to autoimmune disease in mice. Upon formation of complementactivating ICs with natural or disease-associated antibodies, self-antigen binds to B cells via CD21 and CD35 (CR1) and induces proliferation of self-reactive B cells and CD4+ T cells. Here, we review the role of BCR, CD21/ CD19 and Fc?RIIB in regulating B-cell activity in immune and autoimmune responses.

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“…It is possible that immune complexes internalized by CD21 are preferentially targeted to certain intracellular compartments. Such a chaperoning role for C3b has been suggested by studies in which certain antigenic epitopes are presented more efficiently when the antigen is covalently linked to C3b [40]. Additional studies demonstrated that C3b-coated antigens are protected from proteolysis by endosoma1 proteases encountered early in the processing pathway, delaying degradation until entry into lysosomal compartments containing proteases which release the antigen from C3b [41].…”

Section: Discussionmentioning

confidence: 98%

CD21 augments antigen presentation in immune individuals

1997

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CD21 (complement receptor 2, CR2) binds the C3 degradation products, iC3b and C3d, which are covalently linked to antigen or immune complexes in the process of complement activation. The ability of antigen-nonspecific B cells to present immune complexes containing high titers of acquired antibodies was tested. Influenza virus was incubated with serum from immune donors to create complement-containing complexes. These bound specifically to CD21 on transfected fibroblasts and B cell lines, as measured by microcytofluorimetry. Binding of immune complexes was ablated by inactivation of serum complement. In addition, the immunoglobulin in immune human serum blocked influenza binding to cells in the absence of complement, implying a minimal role for immunoglobulin-Fc receptor interactions in this system. Significant immune complex binding required a threshold level of CD21 expression, suggesting that only those cells with the highest levels of CD21 are likely to participate in the processing of macromolecular antigens. B cells pulsed with complement-influenza complexes elicited an augmented response from a panel of influenza-specific, class II-restricted T cell clones, as compared with those which had bound immunoglobulin-influenza complexes lacking complement. This enhanced response did not require CD35. In addition, B cell lines expressing higher levels of CD21 were more efficient in processing antigen than those with lower levels. These findings suggest that presentation of antigen by B cells in immune individuals is dependent on the binding of complement-antigen immune complexes to CD21.

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Covalent binding of C3b to monoclonal antibodies selectively up‐regulates heavy chain epitope recognition by T cells

Cited by 20 publications

References 53 publications

The Role of Complement in Immune and Autoimmune Responses

The Role of Complement in Immune and Autoimmune Responses

Regulation of B-Cell Activation by Complement Receptors and Fc Receptors

CD21 augments antigen presentation in immune individuals

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