{"id":40320,"date":"2025-08-13T00:47:12","date_gmt":"2025-08-12T22:47:12","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/08\/13\/pten-restricts-il-21r-signaling-in-gc-b-cells-and-suppresses-their-differentiation-to-plasma-cells\/"},"modified":"2025-08-13T00:47:12","modified_gmt":"2025-08-12T22:47:12","slug":"pten-restricts-il-21r-signaling-in-gc-b-cells-and-suppresses-their-differentiation-to-plasma-cells","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/08\/13\/pten-restricts-il-21r-signaling-in-gc-b-cells-and-suppresses-their-differentiation-to-plasma-cells\/","title":{"rendered":"PTEN restricts IL-21R signaling in GC B cells and suppresses their differentiation to plasma cells"},"content":{"rendered":"
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J Immunol<\/b>. 2025 Aug 7:vkaf160. doi: 10.1093\/jimmun\/vkaf160. Online ahead of print.<\/p>\n

ABSTRACT<\/b><\/p>\n

The germinal center (GC) reaction is essential for generating high-quality humoral memory. Positively selected GC B cells must decide whether to remain in the GC for further affinity maturation or differentiate into memory or plasma cells (PCs). Previously, we identified IL-21R and CD40 signaling as critical promoters of GC B cell effector differentiation. However, the mechanisms regulating the strength of these signals remain unclear. PTEN, a negative regulator of PI3K signaling, is markedly upregulated in GC B cells. To explore the role of PTEN in GC B cell fate decisions, we used a tamoxifen-driven Cre system to delete PTEN in B cells after GC reaction was fully established. We found that PTEN deletion in ongoing GC B cells led to significantly increased differentiation into PCs, while having limited effects on class switching or memory precursor differentiation. These results were further confirmed using a GC B cell transfer system, where wild-type and PTEN-deficient GC B cells were transferred into the same recipient mice. Mechanistically, PTEN deletion or inhibition in established GC B cells resulted in more sustained IL-21R signaling and enhanced CD40 signaling-both known to promote PC differentiation. Interestingly, Peyer’s patch GC B cells exhibited higher PTEN levels than de novo GC B cells generated through immunization. Notably, PTEN deficiency selectively expanded GC B cells in Peyer’s patches but had no impact on those induced by immunization. These findings reveal previously unrecognized roles for PTEN in regulating GC B cell signaling and limiting their differentiation into PCs.<\/p>\n

PMID:40795247<\/a> | DOI:10.1093\/jimmun\/vkaf160<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"

J Immunol. 2025 Aug 7:vkaf160. doi: 10.1093\/jimmun\/vkaf160. Online ahead of print. ABSTRACT The germinal center (GC) reaction is essential for generating high-quality humoral memory. Positively selected GC B cells must decide whether to remain in the GC for further affinity maturation or differentiate into memory or plasma cells (PCs). Previously, we identified IL-21R and CD40 … 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-40320","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\/40320","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=40320"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/40320\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=40320"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=40320"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=40320"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}