Unusual biochemical features and follicular dendritic cell expression of human Fcα/μ receptor

Kikuno, Kaoru; Kang, Dong‐Won; Tahara, Keishiro; Torii, Ikuko; Kubagawa, Homare M.; Ho, Kang-Jey; Baudino, Lucie Clementine; Nishizaki, Naoto; Shibuya, Akira; Kubagawa, Hiromi

doi:10.1002/eji.200737655

Cited by 60 publications

(50 citation statements)

References 51 publications

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“…In contrast to A7, a protective human IgM MAb to Cryptococcus neoformans GXM, 2E9, was opsonic and promoted fungal killing in vitro (17,54). Given that there is limited evidence for a phagocytic IgM Fc receptor in mice (18,30,47), 2E9-induced phagocytosis was thought to stem from MAb-dependent C3 deposition on GXM, enabling binding to host phagocyte complement receptors (54).…”

Section: Discussionmentioning

confidence: 99%

Aggregation of Streptococcus pneumoniae by a Pneumococcal Capsular Polysaccharide-Specific Human Monoclonal IgM Correlates with Antibody Efficacy In Vivo

Fabrizio

Manix

Guimarães

et al. 2010

Clin Vaccine Immunol

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Acquired antibody immunity to Streptococcus pneumoniae (pneumococcus) has been linked to serotype (ST)-specific opsonic antibodies to the relevant pneumococcal capsular polysaccharide (PPS) that mediate protection by enhancing the bactericidal effect of host phagocytes. Despite the well-recognized role of opsonic IgG in host defense against pneumococcus, PPS-specific monoclonal antibodies (MAbs) that mediate protection against lethal challenge with ST3 pneumococcus in mice but do not promote phagocytic killing in vitro (nonopsonic antibodies) have been described. In this study, we sought to determine the biological activity of one such MAb, A7 (a human PPS3-specific IgM), and the mechanism by which it mediates protection. In vitro studies demonstrated that coincubation of A7 with ST3 in the absence of phagocytes or a complement source resulted in a reduction in CFU on blood agar plates that was largely reversible by sonication. A chromogenic cellular proliferation assay demonstrated that A7 did not affect replication of ST3 in liquid culture. The ability of A7 to induce aggregation of ST3 was confirmed by fluorescence microscopy and flow cytometry: A7 induced aggregation of ST3, and in the presence of a complement source, A7 promoted deposition of complement component 3 (C3) on aggregated bacteria in a dose-dependent fashion. Similarly, administration of preincubated mixtures of A7 and ST3 intraperitoneally to mice protected them from the lethality of ST3 in a dose-dependent fashion. These findings suggest that A7-mediated aggregation enhances resistance to ST3, most likely by enhancing C3 deposition on the ST3 capsule, thereby promoting host antipneumococcal activity in vivo.Despite the availability of antibiotics and two vaccines for Streptococcus pneumoniae (pneumococcus), mortality attributable to pneumococcal disease remains a significant global problem (1, 23). Concerns about ongoing pneumococcal antibiotic resistance, poor vaccine immunogenicity in immunocompromised patients, and serotype (ST) replacement stemming from use of the conjugate vaccine (23,25,29,38) underscore the critical need for a better understanding of correlates of pneumococcal immunity. The efficacy of pneumococcal capsular polysaccharide (PPS)-based vaccines has been linked to their ability to elicit serotype-specific IgG that promotes phagocytosis and killing of the homologous pneumococcal ST in vitro (13,27,43,46). However, given that ST3 has emerged as a replacement ST that causes severe disease (23,25), it is concerning that an investigational conjugate vaccine containing an ST3 moiety did not protect against ST3 disease in children (37). The foregoing, together with evidence that ST3 is associated with a higher risk of severe disease and death than other serotypes (3,23,35), suggests the need for new strategies to prevent disease with ST3.

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Section: Discussionmentioning

confidence: 99%

Aggregation of Streptococcus pneumoniae by a Pneumococcal Capsular Polysaccharide-Specific Human Monoclonal IgM Correlates with Antibody Efficacy In Vivo

Fabrizio

Manix

Guimarães

et al. 2010

Clin Vaccine Immunol

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“…Interestingly, the interaction site of IgA and IgM with the Fc␣/ receptor is confined to the interdomain regions (34) defined for CHIR-AB1 and Fc␣RI, again arguing that these receptors have a common origin. In fact, the Fc␣/ receptor has several features in common with CHIR-AB1, including its single Ig domain, its expression on B lymphocytes, and its high-affinity binding that may be important for rapid receptor recycling to maintain constant plasma levels (35).…”

Section: Discussionmentioning

confidence: 99%

Chicken IgY Binds Its Receptor at the CH3/CH4 Interface Similarly as the Human IgA:FcαRI Interaction

Pürzel

Schmitt

Viertlboeck

et al. 2009

The Journal of Immunology

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Chicken IgY, the ancestral form of mammalian IgE and IgG, is recognized by the high-affinity FcY receptor CHIR-AB1, a member of the leukocyte receptor family. In this study, we have characterized the receptor ligand interaction site by consecutive truncations of the Fcυ IgY domains and mutational analyses of selected residues. Using several fusion proteins that linked the human Cγ2 and Cγ3 domains with the Fcυ IgY domains, a binding assay revealed that both the Fcυ3 and Fcυ4 domains were essential for the IgY CHIR-AB1 interaction. Sequence comparisons of chicken IgY with human IgA demonstrated that 11 of the 19 contact residues important for the IgA FcαRI interaction have been conserved in chicken IgY, although the overall amino acid identity is only 34%. Among the 19 amino acids at respective positions in IgY, the mutation of two residues in the Fcυ3 and two in the Fcυ4 domain completely abolished the IgY to CHIR-AB1 binding revealed by two independent assays. Three further mutations substantially altered the interaction. Molecular modeling on the Cυ3 to Cυ4 crystal structure revealed that all critical residues, although on two domains, are in close proximity. The importance of N-linked carbohydrates was demonstrated by the failure of the CHIR-AB1 interaction after mutation of the glycosylation site. The identification of the IgY Cυ3/Cυ4 interdomain region as critical for binding to CHIR-AB1 significantly enhances our understanding of the IgY receptor interaction and allows further conclusions regarding the FcR phylogeny.

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“…Interestingly, regions with FDCs also exhibited staining with anti-IgM mAb in 7-monthold calves (data not shown) indicating that IgM-antigen or IgM-complement-antigen complexes could be retained by FDCs. This retention may occur through either a complement receptor or the suggested presence of an Fc alpha/mu receptor (Fc␣/R) in cattle similar to humans (Kikuno et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical investigation of cells expressing CD21, membrane IgM, CD32 and a follicular dendritic cell marker in the lymphoid tissues of neonatal calves

Chattha

Hodgins

Delay

et al. 2010

Veterinary Immunology and Immunopathology

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a b s t r a c tActivation of B lymphocytes in the presence of passive maternal antibodies depends on expression of CD21, membrane IgM and CD32. On colligation with IgM, CD32 inhibits activation whereas CD21 enhances it. Recently, we assessed expression of CD21 and CD32 on IgM + cells from lymphoid tissues of newborn calves by flow cytometry, but this approach does not provide information about spatial distribution within lymphoid compartments. Therefore, histologic sections of lymphoid tissues from newborn and 7-month-old calves were examined using an immunoperoxidase technique. In all calves, CD21 and IgM stained cells were collocated in the cortex and paracortex of the retropharyngeal lymph node, in the marginal zone of the spleen and in lymphoid aggregates of palatine tonsils. Most CD32 + cells were in the mantle zone of lymphoid follicles in 7-month-old calves, whereas only weak staining was observed in newborns. A few CD32 + cells were also observed in the paracortex at both ages. Absence of CD32 + cells in the center of follicles suggests that IgM + CD32 − cells observed previously by flow cytometry were from germinal centers. Overall, there were few organized lymphoid aggregates within lymphoid tissues of newborn calves, and follicular dendritic cells were virtually undetectable. Their absence may be an important limitation for neonatal immunization.

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Unusual biochemical features and follicular dendritic cell expression of human Fcα/μ receptor

Cited by 60 publications

References 51 publications

Aggregation of Streptococcus pneumoniae by a Pneumococcal Capsular Polysaccharide-Specific Human Monoclonal IgM Correlates with Antibody Efficacy In Vivo

Aggregation of Streptococcus pneumoniae by a Pneumococcal Capsular Polysaccharide-Specific Human Monoclonal IgM Correlates with Antibody Efficacy In Vivo

Chicken IgY Binds Its Receptor at the CH3/CH4 Interface Similarly as the Human IgA:FcαRI Interaction

Immunohistochemical investigation of cells expressing CD21, membrane IgM, CD32 and a follicular dendritic cell marker in the lymphoid tissues of neonatal calves

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