Feedback regulation by IgG antibodies

Heyman, Birgitta

doi:10.1016/s0165-2478(03)00078-6

Cited by 88 publications

(71 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the role of FcgRIIb as a rheostat for the immune system has been recognized for many years (1,5,6,53), to our knowledge, our report is the first to amplify this signaling pathway by optimizing the natural interaction of Fc with FcgRIIb in the context of IC. In principle, it should be possible to trigger the inhibitory FcgRIIb pathway with other biologic agents.…”

Section: Discussionmentioning

confidence: 88%

“…When sufficient Ab is raised against a given Ag, specific IC form and coengage FcgRIIb and BCR with high avidity, selectively suppressing only B cells recognizing cognate Ag (1). In addition, FcgRIIb regulates activity of other B cell stimulators including IL-4, LPS, and BAFF (2) that amplify BCR-driven proliferation and differentiation, although the signaling mechanisms are currently poorly understood.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Antibody-Mediated Coengagement of FcγRIIb and B Cell Receptor Complex Suppresses Humoral Immunity in Systemic Lupus Erythematosus

Horton

Chu

Ortiz

et al. 2011

The Journal of Immunology

125

111

View full text Add to dashboard Cite

Engagement of the low-affinity Ab receptor FcγRIIb downregulates B cell activation, and its dysfunction is associated with autoimmunity in mice and humans. We engineered the Fc domain of an anti-human CD19 Ab to bind FcγRIIb with high affinity, promoting the coengagement of FcγRIIb with the BCR complex. This Ab (XmAb5871) stimulated phosphorylation of the ITIM of FcγRIIb and suppressed BCR-induced calcium mobilization, proliferation, and costimulatory molecule expression of human B cells from healthy volunteers and systemic lupus erythematosus (SLE) patients, as well as B cell proliferation induced by LPS, IL-4, or BAFF. XmAb5871 suppressed humoral immunity against tetanus toxoid and reduced serum IgM, IgG, and IgE levels in SCID mice engrafted with SLE or healthy human PBMC. XmAb5871 treatment also increased survival of mice engrafted with PBMC from a unique SLE patient. Unlike anti-CD20 Ab, coengagement of FcγRIIb and BCR complex did not promote B cell depletion in human PBMC cultures or in mice. Thus, amplification of the FcγRIIb inhibitory pathway in activated B cells may represent a novel B cell-targeted immunosuppressive therapeutic approach for SLE and other autoimmune diseases that should avoid the complications associated with B cell depletion.

show abstract

Section: Discussionmentioning

confidence: 88%

mentioning

confidence: 99%

Antibody-Mediated Coengagement of FcγRIIb and B Cell Receptor Complex Suppresses Humoral Immunity in Systemic Lupus Erythematosus

Horton

Chu

Ortiz

et al. 2011

The Journal of Immunology

125

111

View full text Add to dashboard Cite

show abstract

“…Pathogen-associated molecular pattern receptors (PAMP) such as TLR9 may activate B cells independent of antigen; moreover, TLR9 acts synergistically with BCR, enhancing proliferation, cytokine and antibody production, 1 thus promoting uncontrolled B cell activation that ultimately results in the development of autoimmunity. Indeed, signaling through the TLR pathway has been implicated in the pathogenesis of autoimmune diseases including RA and SLE.…”

Section: Discussionmentioning

confidence: 99%

“…1 We therefore compared the effect of the control XENP6187 and FcγRIIb-enhanced anti-CD19 antibodies on B cell secretion of IL-6, TNF and IL-10. Both TLR9-stimulated and the synergistic BCR and TLR9-induced IL-6 production were significantly inhibited by XmAb5871 (Fig.…”

Section: Xmab5871 Blocks Cytokine Secretion Induced By Synergistic Bcmentioning

confidence: 99%

See 1 more Smart Citation

Suppression of innate and adaptive B cell activation pathways by antibody coengagement of FcγRIIb and CD19

Szili

Cserhalmi

Bankó

et al. 2014

mAbs

View full text Add to dashboard Cite

Long‐term maternal imprinting of the specific B cell repertoire by maternal antibodies

et al. 2007

View full text Add to dashboard Cite

Maternal antibodies protect newborns whilst they are immunologically immature. This study shows that maternal antibodies can also shape the B cell repertoire of the offspring long after the maternal antibodies themselves become undetectable. V H DJ H gene-targeted (VI10) mice expressing a heavy chain specific for vesicular stomatitis virus (VSV) produce a 20-fold increased spontaneous titer of VSV-neutralizing antibodies. When transferred from mother to offspring, these antibodies prevented accumulation of Ag-specific transitional type 2 and marginal zone B cells with an activated phenotype and favored selection to the B cell follicles. This effect was B cellintrinsic and lasted up to adulthood. The pups nursed by mothers producing specific antibodies developed higher endogenous antibody titers of this specificity which perpetuated the effects of specific B cell selection into the mature follicular compartment, presumably by blocking auto-Ag-dependent development of transitional type 2 B cells in the spleen. This repertoire change was functional, as following infection of adult mice with VSV, those pups that had received specific maternal antibodies as neonates had increased pre-immune titers and mounted strong early IgG neutralizing antibodies.

show abstract

Feedback regulation by IgG antibodies

Cited by 88 publications

References 44 publications

Antibody-Mediated Coengagement of FcγRIIb and B Cell Receptor Complex Suppresses Humoral Immunity in Systemic Lupus Erythematosus

Antibody-Mediated Coengagement of FcγRIIb and B Cell Receptor Complex Suppresses Humoral Immunity in Systemic Lupus Erythematosus

Suppression of innate and adaptive B cell activation pathways by antibody coengagement of FcγRIIb and CD19

Long‐term maternal imprinting of the specific B cell repertoire by maternal antibodies

Contact Info

Product

Resources

About