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Monte Carlo study of b-cell receptor clustering mediated by antigen crosslinking and directed transport

cellular & Molecular Immunology 2011年第3期8卷 255-264页

作者： A Srinivas Reddy Philippos K Tsourkas Subhadip Raychaudhuri Department of biomedical Engineering University of California DavisDavisUSA biophysics Graduate Group University of California DavisDavisUSA Graduate Group in Applied Mathematics University of California DavisDavisUSA

It is known from experiments that in the presence of soluble antigen,b-cell receptors(bCRs)assemble into microclusters and then collect into a macrocluster known as a‘cap’.However,the mechanisms of bCR cluster formation during recognition of soluble antigens remain unclear.In previous work,we demonstrated that effective intrinsic attractions among bCRs can lead to the formation of small microclusters of bCR molecules.The effective intrinsic attractions could be caused by multivalent antigen binding,association with lipid rafts,or other biochemical factors.In the present study,we have developed and studied a Monte Carlo model of bCR clustering mediated by explicit binding and crosslinking of soluble bivalent antigens.Antigen crosslinking is shown to microcluster bCRs in an affinity-dependent manner and also in a biologically relevant timescale;however,antigen crosslinking alone does not appear to be sufficient for the formation of a single macrocluster of receptor molecules.We show that directed transport of bCRs is needed to drive the formation of large macroclusters.We constructed a simple model of directed transport,where bCR molecules diffuse towards the largest cluster or towards a random bCR microcluster,which results in a single macrocluster of receptor molecules.The mechanisms for both types of directed transport are compared using network-based metrics.We also develop and use appropriate network measures to analyze the effect of bCR and antigen concentration on bCR clustering,the stability of the formed clusters over time and the size of bCR–antigen crosslinked chains.

关键词： b-cell activation b-cell receptor cell signaling Monte Carlo simulation receptor clustering

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Homeostasis and regulation of autoreactive b cells

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cellular & Molecular Immunology 2020年第6期17卷 561-569页

作者： Sujin Lee Yeunjung Ko Tae Jin Kim Department of Immunology Sungkyunkwan University School of MedicineSuwon 16419Republic of Korea

In contrast to the previous belief that autoreactive b cells are eliminated from the normal repertoire of b cells,many autoreactive b cells actually escape clonal deletion and develop into mature b cells.These autoreactive b cells in healthy individuals perform some beneficial functions in the host and are homeostatically regulated by regulatory T and b cells or other mechanisms to prevent autoimmune diseases.Autoreactive b-1 cells constitutively produce polyreactive natural antibodies for tissue homeostasis.Recently,autoreactive follicular b cells were reported to participate actively in the germinal center reaction.Furthermore,the selection and usefulness of autoreactive marginal zone(MZ)b cells found in autoimmune diseases are not well understood,although the repertoire of MZ b-cell receptors(bCRs)is presumed to be biased to detect bacterial antigens.In this review,we discuss the autoreactive b-cell populations among all three major b-cell subsets and their regulation in immune responses and diseases.

关键词： b-cell autoreactivity polyreactivity autoreactive antibody b-cell receptor b-1 lymphocyte autoreactive germinal center autoreactive marginal zone b cell

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Human immune repertoire in hepatitis b virus infection

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World Journal of Gastroenterology 2021年第25期27卷 3790-3801页

作者： Qiao Zhan Jing-Hang Xu Yan-Yan Yu Emily Lo KK Felicianna Hani El-Nezami Zheng Zeng Department of Infectious Diseases Peking University First HospitalBeijing 100034China School of biological Sciences University of Hong KongHong KongChina Institute of Public Health and Clinical Nutrition School of MedicineUniversity of Eastern FinlandKuopio FI-70211Finland

Hepatitis b virus(HbV)infection is a public health threat that affects 257 million people worldwide and can progress to liver cirrhosis,liver failure,and hepatocellular carcinoma.The HbV antigen-induced adaptive immune response plays an important role in HbV clearance.Immune repertoire sequencing(IRS)has been used to investigate the molecular mechanisms behind the immune system,find novel ways to treat HbV infection,and evaluate the genetic responses and immune characteristics of individuals infected by HbV or immunized by HbV vaccine.This review summarizes the human immune repertoire analysis methodology,and the application of the IRS in the prediction of HbV infection progression,treatment,and vaccination.

关键词： Immune repertoire T-cell receptor b-cell receptor Hepatitis b virus Chronic viral infection High-throughput sequencing

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