Anti-citrullinated protein antibodies have a low avidity compared with antibodies against recall antigens

Suwannalai, Parawee; Scherer, Hans Ulrich; Woude, Diane van der; Ioan‐Facsinay, Andreea; Zijde, Cornelia M. Jol–van der; Tol, Maarten J.D. van; Drijfhout, Jan W.; Huizinga, Tom W J; Toes, René E. M.; Trouw, Leendert A.

doi:10.1136/ard.2010.135509

Cited by 70 publications

(68 citation statements)

References 30 publications

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“…This is in contrast to the selection of B cells against recall antigens, which is primarily driven by affinity for cognate antigens 7. In fact, the overall low avidity of secreted polyclonal ACPA-IgG is in line with this hypothesis 8. Possibly, ACPA-IgG variable domain glycans interact with glycan receptors in the vicinity of the BCR.…”

mentioning

confidence: 90%

B-cell receptor sequencing of anti-citrullinated protein antibody (ACPA) IgG-expressing B cells indicates a selective advantage for the introduction of N -glycosylation sites during somatic hypermutation

et al. 2017

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mentioning

confidence: 90%

B-cell receptor sequencing of anti-citrullinated protein antibody (ACPA) IgG-expressing B cells indicates a selective advantage for the introduction of N -glycosylation sites during somatic hypermutation

et al. 2017

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“…Plates were incubated with increasing concentrations of sodium thiocyanate (NaSCN) for 15 min, followed by washing with PBS containing 0.05% Tween and incubation with HRP-conjugated antibodies. The avidity of the MCMV-specific antibodies was determined by the ratio of the amount of antibodies bound after elution with different concentrations of NaSCN relative to the amount of antigen bound in the absence of NaSCN (16).…”

Section: Cd70mentioning

confidence: 99%

Viral Persistence Induces Antibody Inflation without Altering Antibody Avidity

Welten

Redeker

Toes

et al. 2016

J Virol

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Antibodies are implicated in long-term immunity against numerous pathogens, and because of this property, antibody induction is the basis for many vaccines. Little is known about the influence of viral persistence on the evolving antibody response. Here, we examined the characteristics of antibody responses to persistent infection by employing the prototypic betaherpesvirus family member cytomegalovirus (CMV) in experimental mouse models. During the course of infection, mouse CMV (MCMV)-specific IgM and IgG responses are elicited; however, IgG levels gradually inflate in the persistent phase of infection while IgM levels are stably maintained. Whereas CD27-CD70 interactions are dispensable, the CD28/B7 costimulatory pathway is critical for the class switching of MCMV-specific IgM-to-IgG B cell responses, which corresponds to the CD28/B7-dependent formation of CD4 ؉ T follicular helper cells (T FH ) and germinal center (GC) B cells. Furthermore, the initial viral inoculum dose dictates the height of the antibody levels during IgG antibody inflation and relates to the induction of long-lived plasma cells and memory B cells. Antibody avidity nonetheless is not altered after the establishment of viral persistence and occurs independently of the inoculum doses. However, repetitive challenge with intact viral particles, accompanied by increased GC reactivity, promotes the development of high-avidity IgG responses with neutralizing capacity. These insights can be used for the rational design of CMV-based vaccines aimed at inducing antibody responses. IMPORTANCE Antibodies provide long-term protection to different pathogens. However, how antibody responses develop during persistent virus infection is not entirely clear.Here, we characterize factors that influence the virus-specific antibody response to persistent CMV. This study describes that during persistent infection, CMV-specific IgM antibody levels are stably maintained while IgG2b and IgG2c levels gradually inflate over time. In contrast, the IgG avidity remains similar after the establishment of viral persistence. The induction of T follicular helper cells and GC B cells requires CD4 ؉ T cell help and CD28/B7 costimulation signals and is essential for the development of CMV-specific IgG antibody responses. Furthermore, neutralizing CMV-specific antibodies appear to develop late after infection, yet the neutralizing capacity can be improved upon repetitive viral challenge that is associated with increased GC reactivity. The results described here could inform the use of CMV-based vaccines and may help to understand how our immune system copes with this persistent virus.T he maintenance of long-lived humoral responses after infection and vaccination is attributed to both long-lived plasma cells that continuously produce antibodies and to memory B cells that are able to form antibody-secreting cells after reexposure (1, 2). Antibodies can protect against numerous pathogens by direct neutralization and/or by supporting effector functions of immune cells (1, ...

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“…Next to isotype usage15 and avidity,16 the fine specificity of an antibody response is also thought to contribute in determining its efficacy 17. It has been shown that ACPA can recognise a variety of citrullinated antigens, including citrullinated fibrinogen (cFib), α-enolase,18 citrullinated vimentin (cVim) and citrullinated myelin-binding protein (cMBP)—the latter mimicking the Sa antigen 19 20.…”

Section: Introductionmentioning

confidence: 99%