{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:51:11Z","timestamp":1790736671404,"version":"4.1.0"},"reference-count":77,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"75","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2022,9,30]]},"abstract":"<jats:p>Gain-of-function (GOF) mutations in CXCR4 cause WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome, characterized by infections, leukocyte retention in bone marrow (BM), and blood leukopenias. B lymphopenia is evident at early progenitor stages, yet why do CXCR4 GOF mutations that cause B (and T) lymphopenia remain obscure? Using a CXCR4 R334X GOF mouse model of WHIM syndrome, we showed that lymphopoiesis is reduced because of a dysregulated mesenchymal stem cell (MSC) transcriptome characterized by a switch from an adipogenic to an osteolineage-prone program with limited lymphopoietic activity. We identify lymphotoxin beta receptor (LT\u03b2R) as a critical pathway promoting interleukin-7 (IL-7) down-regulation in MSCs. Blocking LT\u03b2R or CXCR4 signaling restored IL-7 production and B cell development in WHIM mice. LT\u03b2R blocking also increased production of IL-7 and B cell activating factor (BAFF) in secondary lymphoid organs (SLOs), increasing B and T cell numbers in the periphery. These studies revealed that LT\u03b2R signaling in BM MSCs and SLO stromal cells limits the lymphocyte compartment size.<\/jats:p>","DOI":"10.1126\/sciimmunol.abo3170","type":"journal-article","created":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T17:59:22Z","timestamp":1663955962000},"source":"Crossref","is-referenced-by-count":26,"title":["Dysregulated stem cell niches and altered lymphocyte recirculation cause B and T cell lymphopenia in WHIM syndrome"],"prefix":"10.1126","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6263-1535","authenticated-orcid":true,"given":"Sandra","family":"Zehentmeier","sequence":"first","affiliation":[{"name":"Department of Immunobiology and Yale Stem Cell Center, Yale University School of Medicine, 300 Cedar Street, New Haven, CT, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2851-4391","authenticated-orcid":true,"given":"Vivian 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