{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:36:42Z","timestamp":1790800602651,"version":"4.1.0"},"posted":{"date-parts":[[2026,7,7]]},"group-title":"Immunology","reference-count":74,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["5R37 AI037526"],"award-info":[{"award-number":["5R37 AI037526"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["1UM1AI144462-01"],"award-info":[{"award-number":["1UM1AI144462-01"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2P01AI100148-11"],"award-info":[{"award-number":["2P01AI100148-11"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/006w34k90","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004343","name":"Stavros Niarchos Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004343","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Cancer Research Institute"},{"id":[{"id":"https:\/\/ror.org\/02r3e0967","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,7]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  Immunoglobulin D (IgD) is among the most conserved antibody isotypes, found in virtually all jawed vertebrates\n                  <jats:sup>1<\/jats:sup>\n                  . Unlike other isotypes, IgD contains an unusually long hinge region of up to 160 amino acids that connects the constant and variable regions. Its expression pattern is also conserved; IgD is co-expressed with IgM on transitional and mature na\u00efve B cells. However, the function of IgD has remained enigmatic since its discovery in 1965\n                  <jats:sup>2,3<\/jats:sup>\n                  . Here we present and test a biophysical model positing that IgD increases the entropic cost of bivalent antigen binding. Single-molecule measurements revealed that the antigen-binding arms of IgD are substantially more dynamic than those of IgM, suggesting that cell surface IgD would be energetically penalized in bivalent antigen binding. Consistent with the model and biophysical data, we find that the long hinge compromises antigen capture by IgD B cell receptors (BCRs) compared to IgM BCRs. To determine how the difference in antigen binding impacts immunity, we produced mice that express only IgM and IgD, exclusively IgM or IgD, or IgD with a truncated hinge region. The data indicate that the increased entropic cost of antigen binding imposed by the IgD hinge attenuates negative selection by self-antigen while increasing the affinity-based threshold for positive selection into the germinal center (GC). Together the results indicate that IgD functions physiologically to desensitize B cells to antigen, thereby expanding the B cell repertoire while optimizing affinity-based selection into the GC.\n                <\/jats:p>","DOI":"10.64898\/2026.07.02.735902","type":"posted-content","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T04:50:13Z","timestamp":1783486213000},"source":"Crossref","is-referenced-by-count":1,"title":["Biophysical properties of IgD determine thresholds for self-tolerance and selection into germinal centers"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3803-871X","authenticated-orcid":false,"given":"Lachlan P.","family":"Deimel","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA"},{"name":"Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan A.","family":"Brady","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, St. Jude Children\u2019s Research Hospital, Memphis, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andriy","family":"Goychuk","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela S","family":"Silva Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Uhe","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"MacLean","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Zong","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurine","family":"Binet","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Tenuta","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Shaefer-Babajew","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeliha","family":"Kilic","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, St. Jude Children\u2019s Research Hospital, Memphis, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Gazumyan","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago Y.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Hartweger","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arup K.","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA"},{"name":"Department of Physics, Massachusetts Institute of Technology, Cambridge, MA, USA"},{"name":"Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA"},{"name":"Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2717-9365","authenticated-orcid":false,"given":"Scott C.","family":"Blanchard","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, St. Jude Children\u2019s Research Hospital, Memphis, TN, USA"},{"name":"Department of Chemical Biology and Therapeutics, St. Jude Children\u2019s Research Hospital, Memphis, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel C.","family":"Nussenzweig","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA"},{"name":"Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026071001300471000_2026.07.02.735902v1.1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601407103"},{"key":"2026071001300471000_2026.07.02.735902v1.2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.121.1.171"},{"key":"2026071001300471000_2026.07.02.735902v1.3","unstructured":"Rowe, D. S. , Crabb\u00e9, P. A. & Turner, M. W . Immunoglobulin D in serum, body fluids and lymphoid tissues. Clin. Exp. 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