Mouse IgM Fc Receptor, FCMR, Promotes B Cell Development and Modulates Antigen-Driven Immune Responses

Choi, Seung‐Chul; Wang, Hongsheng; Tian, Linjie; Murakami, Yousuke; Shin, Dong‐Mi; Borrego, Francisco; Morse, Herbert C.; Coligan, John E.

doi:10.4049/jimmunol.1202227

Cited by 72 publications

(132 citation statements)

References 48 publications

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“…Thus, IgM-antigen (Ag) complexes might have an direct role in B cells. In support of this, mice that are deficient in Fc␥R upon immunization exhibited enhanced germinal center B cell and plasma cell responses (32).…”

Section: Discussionmentioning

confidence: 99%

Influenza Virus-Specific Neutralizing IgM Antibodies Persist for a Lifetime

Skountzou¹,

Satyabhama²,

Stavropoulou³

et al. 2014

Clin. Vaccine Immunol.

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c Detection of immunoglobulin M (IgM) antibodies has long been used as an important diagnostic tool for identifying active viral infections, but their relevance in later stages has not been clearly defined in vivo. In this study, we followed the kinetics, longevity, and function of influenza virus-specific IgM antibodies for 2 years following sublethal infection of mice with live mouseadapted A/PR/8/34 virus or immunization with formalin-inactivated virus. These groups mounted robust protective immune responses and survived lethal challenges with 50؋ 50% lethal dose (LD 50 ) mouse-adapted A/PR/8/34 virus 600 days after the primary exposure. Surprisingly, the virus-specific IgM antibodies persisted along with IgG antibodies, and we found a significantly higher number of IgM-positive (IgM ؉ ) virus-specific plasma cells than IgG ؉ plasma cells that persisted for at least 9 months postexposure. The IgM antibodies were functional as they neutralized influenza virus in the presence of complement just as well as IgG antibodies did.

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Section: Discussionmentioning

confidence: 99%

Influenza Virus-Specific Neutralizing IgM Antibodies Persist for a Lifetime

Skountzou¹,

Satyabhama²,

Stavropoulou³

et al. 2014

Clin. Vaccine Immunol.

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“…ANA in the sera of mice were detected using HEp-2 cells on microscope slides (MBL Bion, Des Plaines, IL, USA) as described previously. 61 The fluorescence of ANA was detected by a Zeiss Axio Imager Upright microscope (Carl Zeiss, Thornwood, NY, USA) with a × 20 Zeiss Plan-Neofluar objective. ANA staining intensity was scored in a genotype-blind fashion.…”

Section: Methodsmentioning

confidence: 99%

Enhanced efferocytosis by dendritic cells underlies memory T-cell expansion and susceptibility to autoimmune disease in CD300f-deficient mice

Tian

Lee

et al. 2016

Cell Death Differ

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Homeostasis requires the immunologically silent clearance of apoptotic cells before they become pro-inflammatory necrotic cells. CD300f (CLM-1) is a phosphatidylserine receptor known to positively regulate efferocytosis by macrophages, and CD300f genedeficient mice are predisposed to develop a lupus-like disease. Here we show that, in contrast to CD300f function in macrophages, its expression inhibits efferocytosis by DC, and its deficiency leads to enhanced antigen processing and T-cell priming by these DC. The consequences are the expansion of memory T cells and increased ANA levels in aged CD300f-deficient mice, which predispose CD300f-deficient mice to develop an overt autoimmune disease when exposed to an overload of apoptotic cells, or an exacerbated autoimmunity when combined with FcγRIIB deficiency. Thus, our data demonstrates that CD300f helps to maintain immune homeostasis by promoting macrophage clearance of self-antigens, while conversely inhibiting DC uptake and presentation of self-antigens.

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“…cDNA was synthesized with Qscript cDNA synthesis kit (Quanta Biosciences, Gaithersburg, MD, USA) and quantitative realtime PCR (qRT-PCR) was performed as previously described. 50 Oligonucleotide primers for amplifying murine CD300b, CD300f, MerTK, Axl, BAI1, Stabilin 2 and GAPDH were purchased from Qiagen. Fold change of expression (relative copy number (RCN)) of selected genes was normalized by the expression of the housekeeping gene, GAPDH and calculated with the equation: RCN ¼ E À DCt , where E ¼ efficiency of PCR, and Ct ¼ Ct target À Ct GAPDH.…”

Section: Methodsmentioning

confidence: 99%

CD300b regulates the phagocytosis of apoptotic cells via phosphatidylserine recognition

et al. 2014

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The CD300 receptor family members are a group of molecules that modulate a variety of immune cell processes. We show that mouse CD300b (CLM7/LMIR5), expressed on myeloid cells, recognizes outer membrane-exposed phosphatidylserine (PS) and does not, as previously reported, directly recognize TIM1 or TIM4. CD300b accumulates in phagocytic cups along with F-actin at apoptotic cell contacts, thereby facilitating their engulfment. The CD300b-mediated activation signal is conveyed through CD300b association with the adaptor molecule DAP12, and requires a functional DAP12 ITAM motif. Binding of apoptotic cells promotes the activation of the PI3K-Akt kinase pathway in macrophages, while silencing of CD300b expression diminishes PI3K-Akt kinase activation and impairs efferocytosis. Collectively, our data show that CD300b recognizes PS as a ligand, and regulates the phagocytosis of apoptotic cells via the DAP12 signaling pathway.

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Mouse IgM Fc Receptor, FCMR, Promotes B Cell Development and Modulates Antigen-Driven Immune Responses

Cited by 72 publications

References 48 publications

Influenza Virus-Specific Neutralizing IgM Antibodies Persist for a Lifetime

Influenza Virus-Specific Neutralizing IgM Antibodies Persist for a Lifetime

Enhanced efferocytosis by dendritic cells underlies memory T-cell expansion and susceptibility to autoimmune disease in CD300f-deficient mice

CD300b regulates the phagocytosis of apoptotic cells via phosphatidylserine recognition

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