Michel C. Nussenzweig

Research summary

Studies of dendritic cell (DC) function in steady-state lymphoid tissue showed that DCs both delete self-reactive T cells in the thymus and induce peripheral tolerance by constitutively presenting antigens captured through endocytic receptors on MHC class I and II, with low-dose receptor-targeted antigen producing antigen-specific unresponsiveness rather than priming [1]. Antibody cloning from single human B cells across developmental stages revealed that 55–75% of early immature B cells expressed self-reactive antibodies, including polyreactive and antinuclear specificities, and that two discrete tolerance checkpoints remove most of these clones before they reach the mature naive repertoire [3]. A targeted antigen-delivery system using a monoclonal antibody against the DC-restricted endocytic receptor DEC-205 delivered antigen orders of magnitude more efficiently than free peptide in complete Freund's adjuvant, but T cells activated this way were not polarized to Th1 and instead became unresponsive, defining a route for steady-state tolerance induction by DCs [5]. A review of germinal centers integrated 125 years of anatomical work with intravital imaging to describe how B cell clonal expansion, somatic hypermutation, and affinity-based selection within these structures generate high-affinity antibodies [4]. In life-threatening COVID-19, neutralizing IgG autoantibodies against type I interferons were detected in 101 of 987 patients (against IFN-ω, the 13 IFN-α subtypes, or both) at the onset of critical disease, with no such autoantibodies in 663 asymptomatic or mildly infected individuals, and the autoantibodies neutralized IFN-mediated blockade of SARS-CoV-2 in vitro [2]. Together these results frame dendritic cells and germinal centers as central regulators of self-tolerance and affinity maturation, while implicating preexisting anti-cytokine humoral autoimmunity in severe viral disease.

Recent publications

1. Tolerogenic Dendritic Cells2003 · Annual Review of Immunology · 3100 citationsDOI
2. Autoantibodies against type I IFNs in patients with life-threatening COVID-192020 · Science · 2828 citationsDOI
3. Convergent antibody responses to SARS-CoV-2 in convalescent individuals2020 · Nature · 2136 citationsDOI
4. Predominant Autoantibody Production by Early Human B Cell Precursors2003 · Science · 2060 citationsDOI
5. Germinal Centers2012 · Annual Review of Immunology · 1867 citationsDOI
6. SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies2020 · Nature · 1854 citationsDOI
7. Dendritic Cells Induce Peripheral T Cell Unresponsiveness under Steady State Conditions in Vivo2001 · The Journal of Experimental Medicine · 1819 citationsDOI
8. Evolution of antibody immunity to SARS-CoV-22021 · Nature · 1763 citationsDOI
9. 53BP1 Inhibits Homologous Recombination in Brca1-Deficient Cells by Blocking Resection of DNA Breaks2010 · Cell · 1660 citationsDOI
10. mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants2021 · Nature · 1514 citationsDOI

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Email Michel C. Nussenzweig 6-12 months before your application deadline. Read several recent papers and reference specific work in your message. Use our how to email a Japanese professor guide for the proven email structure.

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External profiles

• ORCID: https://orcid.org/0000-0003-0592-8564
• OpenAlex: openalex.org

Profile compiled from public sources (Researchmap, OpenAlex, Kyoto University faculty directory). Last refreshed 2026-05. Report incorrect information.