Role of Complement in Induction of Antibody Production in Vivo

Pepys, Mark B.

doi:10.1084/jem.140.1.126

Cited by 310 publications

(115 citation statements)

References 43 publications

(47 reference statements)

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“…The first is the central role of complement in induction of immunological memory and normal humoral responses (reviewed in references 13,14). These effects have been ascribed to C3 (14).…”

Section: Resultsmentioning

confidence: 99%

Complement activation is required for IgM-mediated enhancement of the antibody response.

Heyman

Pilström

Shulman

1988

The Journal of Experimental Medicine

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The ability of IgM antibodies to specifically enhance the thymus-dependent humoral immune response to particulate antigens is well documented. We have used two approaches to test whether complement factors play a role in this process. First, mice were depleted of C3 by treatment with cobra venom factor (CVF) and then immunized with SRBC with or without IgM-anti-SRBC. CVF treatment severely impaired the capacity of IgM to induce an enhanced anti-SRBC response. Moreover, it was shown that IgM can potentiate the response in C5-deficient AKR mice, thus demonstrating that the complement factors acting before C5 are the crucial ones. A second test compared the enhancing properties of two monoclonal IgM-anti-TNP antibodies where, because of a point mutation in the mu chain constant region, one of the antibodies is impaired in its capacity to activate complement. We show that the mutant antibody lacks the enhancing properties of the wild-type IgM. Activation of C3 by IgM antibodies as well as localization of antigen in the spleen seem to be necessary steps in the IgM-mediated enhancement of antibody responses. Our data offer an explanation to the immunosuppression described in CVF-treated animals as well as the low humoral immune responses in certain hereditary complement deficiencies. It is suggested that IgM indeed has an important physiological function in enhancing antibody responses to foreign substances.

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“…The first is the central role of complement in induction of immunological memory and normal humoral responses (reviewed in references 13,14). These effects have been ascribed to C3 (14).…”

Section: Resultsmentioning

confidence: 99%

Complement activation is required for IgM-mediated enhancement of the antibody response.

Heyman

Pilström

Shulman

1988

The Journal of Experimental Medicine

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“…1A1-A5). Complement and CR are known to facilitate trapping of IC on FDC [11][12][13][14][15]; thus, IC strongly labeled FDC-reticula in both passively immunized WT and FccRIIB -/-mice. In contrast, neither anti-OVA Ab nor OVA in the presence of nonspecific rabbit serum (NSS) were retained on the FDC-reticula, confirming the importance of the IC.…”

Section: Fdc-mediated Ic Trappingmentioning

confidence: 99%

“…The ability to stimulate B cells depends in large measure on the ability of FDC to trap and present Ag to specific B cells. FDC capture and retain Ag in the form of IC, and starting in the early 1970s, a number of studies elegantly documented that complement and complement receptors (CR) were necessary for optimal IC trapping and retention [11][12][13][14][15]. Although, Fc receptors may not be as important as complement and CR in IC trapping, they do appear to enhance long-term retention of IC by FDC [3].…”

Section: Introductionmentioning

confidence: 99%

Follicular dendritic cell (FDC)‐FcγRIIB engagement via immune complexes induces the activated FDC phenotype associated with secondary follicle development

et al. 2006

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Follicular dendritic cell (FDC)-FccRIIB levels are up-regulated 1-3 days after challenge of actively immunized mice with Ag. This kinetics suggested that memory cells are not driving this response, prompting the hypothesis that immune complex (IC)-FDC interactions lead to FDC activation. To test this, mice passively immunized with anti-OVA Ab were OVA challenged to produce IC. After 3 days, levels of IC, FccRIIB, ICAM-1, and VCAM-1 on FDC were analyzed. FDC were also stimulated with IC in vitro, and mRNA for FccRIIB, ICAM-1, and VCAM-1 was quantified by quantitative RT-PCR. IC labeling in passively immunized WT and FccRIIB -/-mice revealed five to six FDCreticula per LN midsagittal section. In WT mice, these IC-bearing FDC-reticula corresponded with FDC-reticula labeling for FccRIIB, ICAM-1, and VCAM-1. Increases in these molecules on IC-stimulated FDC were confirmed by flow cytometry. In marked contrast, in FccRIIB -/-mice, no increased VCAM-1 or ICAM-1 was seen on IC-bearing FDC-reticula or on purified FDC. Addition of IC in vitro resulted in dramatic increases in mRNA for FccRIIB, ICAM-1 and VCAM-1 in WT FDC, but not in FDC from FccRIIB -/-mice, 2.4G2-pretreated WT FDC, B cells, or macrophages. Thus, although FDC-FccRIIB was not essential for IC trapping, engagement of FDC-FccRIIB with IC initiated an FDC activation pathway.

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“…It was Mark Pepys who, in the 1970s, noted the influence of complement on the adaptive immune response [1]. He found that mice depleted of complement failed to develop potent antibody responses, although the effect was partially overcome by increasing the dose of injected antigen.…”

mentioning

confidence: 99%

Complement fragments C3a and C5a: The salt and pepper of the immune response

Sacks

2010

Eur J Immunol

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The influence of complement on B‐cell responses has been known for many years, but the notion that T‐cell recognition, expansion and differentiation are complement dependent has only recently gained impetus. DC, and to a lesser extent T cells, produce a range of complement components necessary for complement activation, and these cells also express receptors that detect complement‐activation products such as C3a and C5a (anaphylatoxins). In the absence of C3a‐receptor (C3aR) signalling, DC lose their capacity to induce potent Th1 responses against alloantigen and also favour the emergence of Treg. A study in this issue of the European Journal of Immunology not only spotlights the importance of C5aR signalling in DC interaction with T cells, but also shows how cooperation with other signalling pathways determines the outcome of T‐cell activation. Remove C5aR from the equation, TLR2‐stimulated DC induce naive CD4+ Th cells to undergo differentiation not only mainly to Th17 cells but also to Treg, via a TGF‐β‐dependent pathway. Thus, anaphylatoxins in conjunction with other danger signalling pathways modify the function of DC in antigen presentation and help to shape the primary immune response. Future work will need to address the impact of anaphylatoxins on protective immunity in vivo and determine the wider implications of anaphylatoxins for allo‐ and autoimmunity.

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Role of Complement in Induction of Antibody Production in Vivo

Cited by 310 publications

References 43 publications

Complement activation is required for IgM-mediated enhancement of the antibody response.

Complement activation is required for IgM-mediated enhancement of the antibody response.

Follicular dendritic cell (FDC)‐FcγRIIB engagement via immune complexes induces the activated FDC phenotype associated with secondary follicle development

Complement fragments C3a and C5a: The salt and pepper of the immune response

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