{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T01:24:35Z","timestamp":1790040275524,"version":"4.0.1"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":12,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"John Goldman Fellowship Follow-up"},{"DOI":"10.13039\/501100015570","name":"Blood Cancer UK","doi-asserted-by":"publisher","award":["25006"],"award-info":[{"award-number":["25006"]}],"id":[{"id":"10.13039\/501100015570","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Southampton Cancer Immunology Talent Fund"},{"name":"MRC-CARP Fellowship"},{"name":"UK Research and Innovation, Medical Research Council","award":["MR\/T024968\/1"],"award-info":[{"award-number":["MR\/T024968\/1"]}]},{"DOI":"10.13039\/501100012621","name":"UCLH Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012621","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Autoreactive B cells that remain in lymphatic tissue after anti-CD20 antibody therapy are considered a major contributing factor to relapse in patients with autoimmune diseases. Natural killer (NK) cells contribute to the depletion of autoreactive B cells by anti-CD20 antibodies via antibody-dependent cellular cytotoxicity (ADCC). However, the impact of germinal centre\u2013associated signals CD40 ligand (CD40L) and interleukin-4 (IL-4) on ADCC was unknown. This study used a combination of flow cytometry, immunohistochemistry, and ex vivo functional assays using peripheral blood mononuclear cells to investigate how CD40L and IL-4 affect NK cell\u2013B cell interactions. CD40L and IL-4 significantly upregulate human leukocyte antigen (HLA)-E and total HLA Class I expression on the surface of B cells from healthy donors, as well as patients with rheumatoid arthritis and systemic lupus erythematosus. The upregulation of HLA-E and total HLA functions to inhibit B-cell depletion by NK cell\u2013mediated ADCC induced by rituximab via NKG2A and killer cell immunoglobulin-like receptors (KIR). Moreover, B cells that have differentiated through the germinal centre have higher expression of HLA-E and total HLA compared with naive B cells and are more resistant to depletion by rituximab. In accordance with this, blockade of NKG2A and inhibitory KIRs by monalizumab and lirilumab, respectively, increased antibody-dependent cellular cytotoxicity against autologous B cells in vitro. Overall, this study identifies a novel mechanism of resistance of B cells to NK cell cytotoxicity and indicates that blockade of the HLA-E:NKG2A and HLA:KIR checkpoint axes could be beneficial for improving B-cell depletion in patients with autoimmune diseases.<\/jats:p>","DOI":"10.1093\/cei\/uxag001","type":"journal-article","created":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T12:33:02Z","timestamp":1768048382000},"source":"Crossref","is-referenced-by-count":2,"title":["CD40L and IL-4 lymph node-associated signals protect B cells from rituximab-induced ADCC via KIR and NKG2A"],"prefix":"10.1093","volume":"220","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5420-9020","authenticated-orcid":false,"given":"Lara V","family":"Graham","sequence":"first","affiliation":[{"name":"School of Clinical and Experimental Sciences, University of Southampton , Southampton ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell B","family":"Foxall","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences, University of Southampton , Southampton ,","place":["UK"]},{"name":"Antibody and Vaccine Group, Centre for Cancer Immunology, Faculty of Medicine, University of Southampton , Southampton ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Ashton-Key","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences, University of Southampton , Southampton ,","place":["UK"]},{"name":"Antibody and Vaccine Group, Centre for Cancer Immunology, Faculty of Medicine, University of Southampton , Southampton ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4057-9091","authenticated-orcid":false,"given":"Salim I","family":"Khakoo","sequence":"additional","affiliation":[{"name":"School of Clinical and Experimental Sciences, University of Southampton , Southampton 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Rheumatology and Regenerative Medicine, UCL , London ,","place":["UK"]},{"name":"Department of Rheumatology, University College London Hospital , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2077-089X","authenticated-orcid":false,"given":"Mark S","family":"Cragg","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences, University of Southampton , Southampton ,","place":["UK"]},{"name":"Antibody and Vaccine Group, Centre for Cancer Immunology, Faculty of Medicine, University of Southampton , Southampton ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1099-3985","authenticated-orcid":false,"given":"Matthew D","family":"Blunt","sequence":"additional","affiliation":[{"name":"School of Clinical and Experimental Sciences, University of Southampton , Southampton 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