---
title: "IL-2 and CD40L drive TIGIT+ class-switched memory B cells with regulatory function"
id: "biorxiv-23-il-2-and-cd40l-can-establish-and-sustain-a-human-b-cell-mediated-immune"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-23-il-2-and-cd40l-can-establish-and-sustain-a-human-b-cell-mediated-immune"
content_type: "clinical_feed_article"
specialty: "Hematology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.12.755729v1?rss=1"
published_at: "2026-10-18T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# IL-2 and CD40L drive TIGIT+ class-switched memory B cells with regulatory function
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-23-il-2-and-cd40l-can-establish-and-sustain-a-human-b-cell-mediated-immune
- **Specialty:** [Hematology](https://medichelpline.com/clinical-feed/hematology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.12.755729v1?rss=1)
- **Published At:** 2026-10-18T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Investigators reported that combined **IL-2** and **CD40L** stimulation converts human class-switched memory (CSM) B cells into an immunosuppressive population marked by surface **TIGIT** and multiple inhibitory receptors. - The induced cells also expressed other checkpoint molecules detected by the study team: PD-1, LAG-3, GITR, CD39, and CTLA-4. - Data indicated that these B cells secreted soluble immunoregulatory factors, including **IL-10**, granzyme B, and IL-35, as observed in the authors' assays. - The cohort of TIGIT+ CSM B cells showed a functional chemokine receptor profile; authors noted expression of CCR9 on TIGIT+ cells. - The study team observed that TIGIT+ CSM B cells had pronounced defects in total immunoglobulin secretion but retained secretion of **IgA2**, a selective preservation of antibody output. - Ex vivo-generated TIGIT+ CSM B cells suppressed human T cell–mediated inflammation in a xenogeneic mouse model of acute **graft‑versus‑host disease** and promoted IL-10–producing regulatory T cell responses in that model. - The authors interpreted these findings as identifying **IL-2/CD40L** signaling as drivers of a human B cell–mediated immune regulatory network and suggested the potential to develop TIGIT+ B cell–based therapies for inflammatory diseases. - This report is a preprint; the article has not been peer reviewed. The preprint did not report detailed experimental dosing regimens, sample sizes, or extended methodology in the abstract; such specifics were not provided in the abstract text.
## Clinical Analysis & Structured Key Points
IL-2 and CD40L can establish and sustain a human B cell-mediated immune regulatory network | bioRxiv Skip to main content New Results IL-2 and CD40L can establish and sustain a human B cell-mediated immune regulatory network View ORCID Profile Laurie Baert , Adrien Caffiers , Agnes Yang , SaeRome Choi , View ORCID Profile Suman Bose , Sangkon Oh doi: https://doi.org/10.64898/2026.10.12.755729 Laurie Baert 1 Mayo clinic; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Laurie Baert Adrien Caffiers 1 Mayo clinic; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Agnes Yang 1 Mayo clinic; Find this author on Google Scholar Find this author on PubMed Search for this author on this site SaeRome Choi 1 Mayo clinic; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Suman Bose 2 Mayo Clinic Arizona Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Suman Bose Sangkon Oh 1 Mayo clinic; Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: oh.sangkon{at}mayo.edu Abstract Info/History Metrics Supplementary material Data/Code Preview PDF Abstract B cells can control inflammation, but the factors governing B cell-mediated immune regulatory network remain unclear. We report that IL-2/CD40L enable class-switched memory (CSM) B cells to acquire an immunosuppressive phenotype characterized by the expression of surface TIGIT as well as multiple other inhibitory receptors (PD-1, LAG-3, GITR, CD39, and CTLA-4) and soluble molecules (IL-10, granzyme B, and IL-35). TIGIT+ CSM B cells expressing functional CCR9 exhibit significant defects in total immunoglobulin secretion, while preserving IgA2 secretion. Furthermore, IL-2/CD40L-induced ex vivo-generated TIGIT+ CSM B cells suppress human T cell-mediated inflammation in a xenogeneic mouse model of acute graft-versus-host disease, while promoting IL-10-producing regulatory T cell (Treg) response. These findings identify IL-2/CD40L as key drivers of a B cell-mediated immune regulatory network, especially by generating TIGIT+ CSM B cells that can further promote Treg response. This study supports the development of TIGIT+ B cell-based therapy models for inflammatory diseases. Competing Interest Statement The authors have declared no competing interest. Footnotes https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi Funder Information Declared National Institutes of Health, https://ror.org/01cwqze88 , 1R21AI190763-01A1 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Back to top Previous Next Posted October 18, 2026. Download PDF Supplementary Material Data/Code Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. 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Share IL-2 and CD40L can establish and sustain a human B cell-mediated immune regulatory network Laurie Baert , Adrien Caffiers , Agnes Yang , SaeRome Choi , Suman Bose , Sangkon Oh bioRxiv 2026.10.12.755729; doi: https://doi.org/10.64898/2026.10.12.755729 Share This Article: Copy Citation Tools IL-2 and CD40L can establish and sustain a human B cell-mediated immune regulatory network Laurie Baert , Adrien Caffiers , Agnes Yang , SaeRome Choi , Suman Bose , Sangkon Oh bioRxiv 2026.10.12.755729; doi: https://doi.org/10.64898/2026.10.12.755729 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Areas All Articles Animal Behavior and Cognition (8154) Biochemistry (19000) Bioengineering (15136) Bioinformatics (45156) Biophysics (22922) Cancer Biology (20045) Cell Biology (27238) Clinical Trials (138) Developmental Biology (14115) Ecology (21352) Epidemiology (2067) Evolutionary Biology (25746) Genetics (16307) Genomics (23783) Immunology (18968) Microbiology (43106) Molecular Biology (18287) Neuroscience (94826) Paleontology (710) Pathology (3024) Pharmacology and Toxicology (5171) Physiology (8254) Plant Biology (16225) Scientific Communication and Education (2113) Synthetic Biology (4630) Systems Biology (10361) Zoology (2417)
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