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Supportive to CLL cell survival is chronic B\u2010cell receptor (BCR) signalling; however, emerging evidence demonstrates CLL cells proliferate in response to T\u2010helper (Th) cells in a CD40L\u2010dependent manner. We showed provision of Th stimulation via CD40L upregulated CD45 phosphatase activity and BCR signalling in non\u2010malignant B cells. Consequently, we hypothesised Th cell upregulation of CLL cell CD45 activity may be an important regulator of CLL BCR signalling and proliferation. Using patient\u2010derived CLL cells in a culture system with activated autologous Th cells, results revealed increases in both Th and CLL cell CD45 activity, which correlated with enhanced downstream antigen receptor signalling and proliferation. Concomitantly increased was the surface expression of Galectin\u20101, a CD45 ligand, and CD43, a CLL immunophenotypic marker. Galectin\u20101\/CD43 double expression defined a proliferative CLL cell population with enhanced CD45 activity. Targeting either Galectin\u20101 or CD43 using silencing, pharmacology, or monoclonal antibody strategies dampened CD45 activity and CLL cell proliferation. These results highlight a mechanism where activated Th cells drive CLL cell BCR signalling and proliferation via Galectin\u20101 and CD43\u2010mediated regulation of CD45 activity, identifying modulation of CD45 phosphatase activity as a potential therapeutic target in CLL.<\/jats:p>","DOI":"10.1111\/bjh.18285","type":"journal-article","created":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T04:35:28Z","timestamp":1654230928000},"page":"556-573","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["T\u2010helper cell regulation of <scp>CD45<\/scp> phosphatase activity by galectin\u20101 and <scp>CD43<\/scp> governs chronic lymphocytic leukaemia proliferation"],"prefix":"10.1111","volume":"198","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0809-3550","authenticated-orcid":false,"given":"John F.","family":"Imbery","sequence":"first","affiliation":[{"name":"Department of Immunology Oslo University Hospital  Oslo 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