{"id":67251,"date":"2026-06-11T12:00:49","date_gmt":"2026-06-11T10:00:49","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/06\/11\/variable-fab-domain-n-glycosylation-patterns-in-the-b-cell-receptor-repertoires-of-healthy-individuals-and-patients-with-rheumatoid-arthritis\/"},"modified":"2026-06-11T12:00:49","modified_gmt":"2026-06-11T10:00:49","slug":"variable-fab-domain-n-glycosylation-patterns-in-the-b-cell-receptor-repertoires-of-healthy-individuals-and-patients-with-rheumatoid-arthritis","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/06\/11\/variable-fab-domain-n-glycosylation-patterns-in-the-b-cell-receptor-repertoires-of-healthy-individuals-and-patients-with-rheumatoid-arthritis\/","title":{"rendered":"Variable fab domain N-glycosylation patterns in the B cell receptor repertoires of healthy individuals and patients with rheumatoid arthritis"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2026 Jun 7;215(6):vkag113. doi: 10.1093\/jimmun\/vkag113.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>N-linked glycosylation (N-glyc) sites (N-X-S\/T, X\u2260P) can be introduced by somatic hypermutation in immunoglobulin Fab regions. In patients with rheumatoid arthritis (RA), anti-citrullinated protein antibodies have a striking overrepresentation of Fab N-glycosylation. To further explore this, we sequenced B cell receptors (BCRs) from peripheral blood of 13 RA patients and 6 healthy control subjects, analyzing in total &gt;250,000 heavy chain (VH) and &gt;100,000 light chain sequences from both total B cells and citrullinated fibrinogen-reactive (Cit-Fib+) cells. Distribution of variable VH genes in VDJ DNA, and transcripts of unmutated IgM and class-switched BCR, revealed transcript gene-usage bias and higher VH4 in natural rearrangements by out-of-frame VDJ DNA in RA patients compared with control subjects. IgG Fab N-glyc sites were slightly more prominent in RA than control subjects (14.9% versus 12.1%; P = 0.048) with certain VH genes (e.g. VH1-18, VH1-69, VH3-9) displaying enriched N-glyc cumulative frequencies by somatic hypermutation. VH gene N-glyc hotspots were identified, explained by a lower threshold for codon conversion (i.e. K\/S\/T-X-S\/T) and especially frequent in VH4s. Yet, RA patients had significantly more N-glyc in complementarity-determining region (CDR) 1 and 3 compared with control subjects. Expanded clonotypes with somatic hypermutation-induced N-glyc sites were delineated by network analysis in both the RA patients and control group, but patients with RA displayed more highly mutated class-switched members. Furthermore, Cit-Fib+ BCR-expanded clonotypes could be traced in the total B cell repertoire and exhibited increased frequency of N-glyc in mutated IgG\/IgA subsets. Our findings highlight how Fab N-glyc sites can be linked to biased clonotype evolution and B cell selection in chronic responses.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42269014\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20260611060048&amp;v=2.20.0\">42269014<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkag113\">10.1093\/jimmun\/vkag113<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2026 Jun 7;215(6):vkag113. doi: 10.1093\/jimmun\/vkag113. ABSTRACT N-linked glycosylation (N-glyc) sites (N-X-S\/T, X\u2260P) can be introduced by somatic hypermutation in immunoglobulin Fab regions. In patients with rheumatoid arthritis (RA), anti-citrullinated protein antibodies have a striking overrepresentation of Fab N-glycosylation. To further explore this, we sequenced B cell receptors (BCRs) from peripheral blood of 13 &#8230; <a title=\"Variable fab domain N-glycosylation patterns in the B cell receptor repertoires of healthy individuals and patients with rheumatoid arthritis\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/06\/11\/variable-fab-domain-n-glycosylation-patterns-in-the-b-cell-receptor-repertoires-of-healthy-individuals-and-patients-with-rheumatoid-arthritis\/\" aria-label=\"Read more about Variable fab domain N-glycosylation patterns in the B cell receptor repertoires of healthy individuals and patients with rheumatoid arthritis\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[42,71],"tags":[],"class_list":["post-67251","post","type-post","status-publish","format-standard","hentry","category-publicaciones","category-the-journal-of-immunology"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/67251","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=67251"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/67251\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=67251"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=67251"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=67251"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}