CD72 negatively regulates B lymphocyte responses to the lupus-related endogenous toll-like receptor 7 ligand Sm/RNP

Akatsu, Chizuru; Shinagawa, Kenro; Numoto, Nobutaka; Liu, Zhihong; Ucar, Ayse Konuskan; Aslam, Mohammad; Phoon, Shirly; Adachi, Takahiro; Furukawa, Koji; Ito, Nobuyasu; Tsubata, Takeshi

doi:10.1084/jem.20160560

Cited by 47 publications

(58 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We find that CD72, an inhibitory co-receptor, is downregulated in naïve ACPA B cells relative to RF and Tet − B cells. This may enable transduction of activating B cell signals that override tolerogenic signals received by ACPA B cells (43). Expression of the co-receptor CD21 was down-regulated between naïve ACPA and Tet − cells, as well, though this effect was not significant in our study.…”

Section: Discussionmentioning

confidence: 99%

T Cell–Dependent Affinity Maturation and Innate Immune Pathways Differentially Drive Autoreactive B Cell Responses in Rheumatoid Arthritis

McDavid

Kongpachith

et al. 2018

Arthritis & Rheumatology

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

T Cell–Dependent Affinity Maturation and Innate Immune Pathways Differentially Drive Autoreactive B Cell Responses in Rheumatoid Arthritis

McDavid

Kongpachith

et al. 2018

Arthritis & Rheumatology

View full text Add to dashboard Cite

show abstract

“…Thus, mechanisms intrinsic to TLR7 may not completely distinguish self-RNA from microbial RNA and CD72 is required for complete suppression of responses to self-RNA. CD72 appears to recognize RNA-related self-antigens but not microbial RNA 67 . Microbial RNA is thus distinguished from self-RNA by both mechanisms intrinsic in NA sensors and specific recognition of NA-containing self-antigen by CD72.…”

Section: Nuclear Antigen-specific Tolerance Mechanismmentioning

confidence: 99%

“…Among various B-cell inhibitory co-receptors that activate SHP-1, CD72 plays a unique role in specifically tolerizing B cells reactive to nuclear antigens 67 . Recently, Akatsu et al .…”

Section: Nuclear Antigen-specific Tolerance Mechanismmentioning

confidence: 99%

“…Recently, Akatsu et al . demonstrated that CD72 specifically binds to Sm/RNP and that CD72-mediated signal inhibition is induced when B cells interact with Sm/RNP through BCR, leading to inhibition of B-cell responses to Sm/RNP ( Figure 1) 67 . Sm/RNP may co-ligate Sm/RNP-reactive BCR and CD72, thereby inducing phosphorylation of the CD72 ITIM by Lyn associated with BCR, the event required for SHP-1 activation and signal suppression 54 .…”

Section: Nuclear Antigen-specific Tolerance Mechanismmentioning

confidence: 99%

See 1 more Smart Citation

B-cell tolerance and autoimmunity

Tsubata

2017

F1000Res

Self Cite

View full text Add to dashboard Cite

Self-reactive B cells are tolerized at various stages of B-cell development and differentiation, including the immature B-cell stage (central tolerance) and the germinal center (GC) B-cell stage, and B-cell tolerance involves various mechanisms such as deletion, anergy, and receptor editing. Self-reactive B cells generated by random immunoglobulin variable gene rearrangements are tolerized by central tolerance and anergy in the periphery, and these processes involve apoptosis regulated by Bim, a pro-apoptotic member of the Bcl-2 family, and regulation of B-cell signaling by various phosphatases, including SHIP-1 and SHP-1. Self-reactive B cells generated by somatic mutations during GC reaction are also eliminated. Fas is not directly involved in this process but prevents persistence of GC reaction that allows generation of less stringently regulated B cells, including self-reactive B cells. Defects in self-tolerance preferentially cause lupus-like disease with production of anti-nuclear antibodies, probably due to the presence of a large potential B-cell repertoire reactive to nucleic acids and the presence of nucleic acid-induced activation mechanisms in various immune cells, including B cells and dendritic cells. A feed-forward loop composed of anti-nuclear antibodies produced by B cells and type 1 interferons secreted from nucleic acid-activated dendritic cells plays a crucial role in the development of systemic lupus erythematosus.

show abstract

“…This demonstrates that restraint of autoreactive B cells in the face of chronic autoantigen stimulation requires continuous inhibitory tone. Multiple ITIM-containing receptors maintain inhibitory tone on B cells in vivo , but each may do so in response to distinct types of antigens, such as sialic acids (CD22) [48] immune complexes (FcγRIIB) [49], and Sm/RNP (CD72) [50]. …”

Section: Introductionmentioning

confidence: 99%

Control of autoreactive B cells by IgM and IgD B cell receptors: maintaining a fine balance

Noviski

Zikherman

2018

Current Opinion in Immunology

View full text Add to dashboard Cite

A substantial fraction of mature naïve B cells recognize endogenous antigens, and this autoreactivity must be controlled to prevent autoantibody secretion. Selective downregulation of the IgM BCR on autoreactive B cells has long been appreciated, and recent findings illustrate how this might impose tolerance. The BCR isotype maintained on autoreactive B cells, IgD, is less sensitive to endogenous antigens than IgM. This reduced sensitivity may be conferred by structural properties of IgD and/or differential association with activating and inhibitory co-receptors. Once activated, autoreactive B cells are normally excluded from rapid plasma cell responses, but they can enter the germinal center and lose their autoreactivity through a mutation-selection process termed clonal redemption.

show abstract

CD72 negatively regulates B lymphocyte responses to the lupus-related endogenous toll-like receptor 7 ligand Sm/RNP

Abstract: Akatsu and colleagues show that CD72 specifically recognizes Sm/RNP, a lupus-related self-antigen and an endogenous TLR7 ligand, and inhibits B cell responses to Sm/RNP. In mice, CD72 prevents production of anti-Sm/RNP antibodies crucial for lupus development.

Cited by 47 publications

References 72 publications

T Cell–Dependent Affinity Maturation and Innate Immune Pathways Differentially Drive Autoreactive B Cell Responses in Rheumatoid Arthritis

T Cell–Dependent Affinity Maturation and Innate Immune Pathways Differentially Drive Autoreactive B Cell Responses in Rheumatoid Arthritis

B-cell tolerance and autoimmunity

Control of autoreactive B cells by IgM and IgD B cell receptors: maintaining a fine balance

Contact Info

Product

Resources

About